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<ul id="toc-Exocytosis-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Forms_of_Cell_Signaling" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Forms_of_Cell_Signaling"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2</span> <span>Forms of Cell Signaling</span> </div> </a> <ul id="toc-Forms_of_Cell_Signaling-sublist" class="vector-toc-list"> <li id="toc-Autocrine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Autocrine"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.1</span> <span>Autocrine</span> </div> </a> <ul id="toc-Autocrine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Intracrine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Intracrine"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.2</span> <span>Intracrine</span> </div> </a> <ul id="toc-Intracrine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Juxtacrine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Juxtacrine"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.3</span> <span>Juxtacrine</span> </div> </a> <ul id="toc-Juxtacrine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Paracrine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Paracrine"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.4</span> <span>Paracrine</span> </div> </a> <ul id="toc-Paracrine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Endocrine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Endocrine"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.5</span> <span>Endocrine</span> </div> </a> <ul id="toc-Endocrine-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-Receptors" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Receptors</span> </div> </a> <button aria-controls="toc-Receptors-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Receptors subsection</span> </button> <ul id="toc-Receptors-sublist" class="vector-toc-list"> <li id="toc-Cell_surface_receptors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cell_surface_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1</span> <span>Cell surface receptors</span> </div> </a> <ul id="toc-Cell_surface_receptors-sublist" class="vector-toc-list"> <li id="toc-Ion_channel_linked_receptors" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Ion_channel_linked_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.1</span> <span>Ion channel linked receptors</span> </div> </a> <ul id="toc-Ion_channel_linked_receptors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-G_protein–coupled_receptors" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#G_protein–coupled_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.2</span> <span>G protein–coupled receptors</span> </div> </a> <ul id="toc-G_protein–coupled_receptors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Enzyme-linked_receptors" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Enzyme-linked_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.3</span> <span>Enzyme-linked receptors</span> </div> </a> <ul id="toc-Enzyme-linked_receptors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Intracellular_receptors" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Intracellular_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.4</span> <span>Intracellular receptors</span> </div> </a> <ul id="toc-Intracellular_receptors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Steroid_hormone_receptor" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Steroid_hormone_receptor"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.5</span> <span>Steroid hormone receptor</span> </div> </a> <ul id="toc-Steroid_hormone_receptor-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-Mechanisms_of_Receptor_Down-Regulation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Mechanisms_of_Receptor_Down-Regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Mechanisms of Receptor Down-Regulation</span> </div> </a> <ul id="toc-Mechanisms_of_Receptor_Down-Regulation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Signal_transduction_pathways" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Signal_transduction_pathways"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>Signal transduction pathways</span> </div> </a> <button aria-controls="toc-Signal_transduction_pathways-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Signal transduction pathways subsection</span> </button> <ul id="toc-Signal_transduction_pathways-sublist" class="vector-toc-list"> <li id="toc-Short-term_cellular_responses" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Short-term_cellular_responses"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.1</span> <span>Short-term cellular responses</span> </div> </a> <ul id="toc-Short-term_cellular_responses-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Regulating_gene_activity" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Regulating_gene_activity"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2</span> <span>Regulating gene activity</span> </div> </a> <ul id="toc-Regulating_gene_activity-sublist" class="vector-toc-list"> <li id="toc-Notch_signaling_pathway" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Notch_signaling_pathway"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2.1</span> <span>Notch signaling pathway</span> </div> </a> <ul id="toc-Notch_signaling_pathway-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>See also</span> </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Further_reading" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Further_reading"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>Further reading</span> </div> </a> <ul id="toc-Further_reading-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> <span class="vector-toc-numb">9</span> <span>External links</span> </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label id="vector-page-titlebar-toc-label" for="vector-page-titlebar-toc-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " 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Available in 35 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-35" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">35 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%AA%D8%A3%D8%B4%D9%8A%D8%B1_%D8%A7%D9%84%D8%AE%D9%84%D9%8A%D8%A9" title="تأشير الخلية – Arabic" lang="ar" hreflang="ar" data-title="تأشير الخلية" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-bn mw-list-item"><a href="https://bn.wikipedia.org/wiki/%E0%A6%95%E0%A7%8B%E0%A6%B7%E0%A7%80%E0%A6%AF%E0%A6%BC_%E0%A6%B8%E0%A6%99%E0%A7%8D%E0%A6%95%E0%A7%87%E0%A6%A4_%E0%A6%AA%E0%A7%8D%E0%A6%B0%E0%A7%87%E0%A6%B0%E0%A6%A3_%E0%A6%93_%E0%A6%97%E0%A7%8D%E0%A6%B0%E0%A6%B9%E0%A6%A3" title="কোষীয় সঙ্কেত প্রেরণ ও গ্রহণ – Bangla" lang="bn" hreflang="bn" data-title="কোষীয় সঙ্কেত প্রেরণ ও গ্রহণ" data-language-autonym="বাংলা" data-language-local-name="Bangla" class="interlanguage-link-target"><span>বাংলা</span></a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/%C4%86elijska_komunikacija" title="Ćelijska komunikacija – Bosnian" lang="bs" hreflang="bs" data-title="Ćelijska komunikacija" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Comunicaci%C3%B3_cel%C2%B7lular" title="Comunicació cel·lular – Catalan" lang="ca" hreflang="ca" data-title="Comunicació cel·lular" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Bun%C4%9B%C4%8Dn%C3%A1_signalizace" title="Buněčná signalizace – Czech" lang="cs" hreflang="cs" data-title="Buněčná signalizace" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target"><span>Čeština</span></a></li><li class="interlanguage-link interwiki-da mw-list-item"><a href="https://da.wikipedia.org/wiki/Cellesignalering" title="Cellesignalering – Danish" lang="da" hreflang="da" data-title="Cellesignalering" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target"><span>Dansk</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Comunicaci%C3%B3n_celular" title="Comunicación celular – Spanish" lang="es" hreflang="es" data-title="Comunicación celular" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-eo mw-list-item"><a href="https://eo.wikipedia.org/wiki/%C4%88ela_signalado" title="Ĉela signalado – Esperanto" lang="eo" hreflang="eo" data-title="Ĉela signalado" data-language-autonym="Esperanto" data-language-local-name="Esperanto" class="interlanguage-link-target"><span>Esperanto</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D9%BE%DB%8C%D8%A7%D9%85%E2%80%8C%D8%B1%D8%B3%D8%A7%D9%86%DB%8C_%D8%B3%D9%84%D9%88%D9%84%DB%8C" title="پیام‌رسانی سلولی – Persian" lang="fa" hreflang="fa" data-title="پیام‌رسانی سلولی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Signalisation_cellulaire" title="Signalisation cellulaire – French" lang="fr" hreflang="fr" data-title="Signalisation cellulaire" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Sinalizaci%C3%B3n_celular" title="Sinalización celular – Galician" lang="gl" hreflang="gl" data-title="Sinalización celular" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EC%84%B8%ED%8F%AC_%EC%8B%A0%ED%98%B8%EC%A0%84%EB%8B%AC" title="세포 신호전달 – Korean" lang="ko" hreflang="ko" data-title="세포 신호전달" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D4%B2%D5%BB%D5%BB%D5%A1%D5%B5%D5%AB%D5%B6_%D5%A1%D5%A6%D5%A4%D5%A1%D5%B6%D5%B7%D5%A1%D5%B6" title="Բջջային ազդանշան – Armenian" lang="hy" hreflang="hy" data-title="Բջջային ազդանշան" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target"><span>Հայերեն</span></a></li><li class="interlanguage-link interwiki-hi mw-list-item"><a href="https://hi.wikipedia.org/wiki/%E0%A4%B8%E0%A5%87%E0%A4%B2_%E0%A4%B8%E0%A4%BF%E0%A4%97%E0%A5%8D%E0%A4%A8%E0%A4%B2%E0%A4%BF%E0%A4%82%E0%A4%97" title="सेल सिग्नलिंग – Hindi" lang="hi" hreflang="hi" data-title="सेल सिग्नलिंग" data-language-autonym="हिन्दी" data-language-local-name="Hindi" class="interlanguage-link-target"><span>हिन्दी</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Persinyalan_sel" title="Persinyalan sel – Indonesian" lang="id" hreflang="id" data-title="Persinyalan sel" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Segnalazione_cellulare" title="Segnalazione cellulare – Italian" lang="it" hreflang="it" data-title="Segnalazione cellulare" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%AA%D7%A7%D7%A9%D7%95%D7%A8%D7%AA_%D7%AA%D7%90%D7%99%D7%AA_(%D7%91%D7%99%D7%95%D7%9C%D7%95%D7%92%D7%99%D7%94)" title="תקשורת תאית (ביולוגיה) – Hebrew" lang="he" hreflang="he" data-title="תקשורת תאית (ביולוגיה)" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target"><span>עברית</span></a></li><li class="interlanguage-link interwiki-hu mw-list-item"><a href="https://hu.wikipedia.org/wiki/Sejtkommunik%C3%A1ci%C3%B3" title="Sejtkommunikáció – Hungarian" lang="hu" hreflang="hu" data-title="Sejtkommunikáció" data-language-autonym="Magyar" data-language-local-name="Hungarian" class="interlanguage-link-target"><span>Magyar</span></a></li><li class="interlanguage-link interwiki-mn mw-list-item"><a href="https://mn.wikipedia.org/wiki/%D0%AD%D1%81%D0%B8%D0%B9%D0%BD_%D0%B4%D0%BE%D1%85%D0%B8%D0%BE%D0%BB%D0%BE%D0%BB" title="Эсийн дохиолол – Mongolian" lang="mn" hreflang="mn" data-title="Эсийн дохиолол" data-language-autonym="Монгол" data-language-local-name="Mongolian" class="interlanguage-link-target"><span>Монгол</span></a></li><li class="interlanguage-link interwiki-ja badge-Q70893996 mw-list-item" title=""><a href="https://ja.wikipedia.org/wiki/%E7%B4%B0%E8%83%9E%E3%82%B7%E3%82%B0%E3%83%8A%E3%83%AB%E4%BC%9D%E9%81%94" title="細胞シグナル伝達 – Japanese" lang="ja" hreflang="ja" data-title="細胞シグナル伝達" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Sygnalizacja_kom%C3%B3rkowa" title="Sygnalizacja komórkowa – Polish" lang="pl" hreflang="pl" data-title="Sygnalizacja komórkowa" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Sinaliza%C3%A7%C3%A3o_celular" title="Sinalização celular – Portuguese" lang="pt" hreflang="pt" data-title="Sinalização celular" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ru badge-Q70894304 mw-list-item" title=""><a href="https://ru.wikipedia.org/wiki/%D0%9F%D0%B5%D1%80%D0%B5%D0%B4%D0%B0%D1%87%D0%B0_%D1%81%D0%B8%D0%B3%D0%BD%D0%B0%D0%BB%D0%B0_%D0%B2_%D0%BA%D0%BB%D0%B5%D1%82%D0%BA%D0%B5" title="Передача сигнала в клетке – Russian" lang="ru" hreflang="ru" data-title="Передача сигнала в клетке" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Cell_signaling" title="Cell signaling – Simple English" lang="en-simple" hreflang="en-simple" data-title="Cell signaling" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target"><span>Simple English</span></a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Celi%C4%8Dno_signaliziranje" title="Celično signaliziranje – Slovenian" lang="sl" hreflang="sl" data-title="Celično signaliziranje" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target"><span>Slovenščina</span></a></li><li class="interlanguage-link interwiki-ckb mw-list-item"><a href="https://ckb.wikipedia.org/wiki/%D8%B3%DB%8C%DA%AF%D9%86%D8%A7%DA%B5%DB%8C_%D8%AE%D8%A7%D9%86%DB%95%DA%A9%D8%A7%D9%86" title="سیگناڵی خانەکان – Central Kurdish" lang="ckb" hreflang="ckb" data-title="سیگناڵی خانەکان" data-language-autonym="کوردی" data-language-local-name="Central Kurdish" class="interlanguage-link-target"><span>کوردی</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/%D0%8B%D0%B5%D0%BB%D0%B8%D1%98%D1%81%D0%BA%D0%B0_%D0%BA%D0%BE%D0%BC%D1%83%D0%BD%D0%B8%D0%BA%D0%B0%D1%86%D0%B8%D1%98%D0%B0" title="Ћелијска комуникација – Serbian" lang="sr" 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</div> </div> <div id="bodyContent" class="vector-body" aria-labelledby="firstHeading" data-mw-ve-target-container> <div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"><span class="mw-redirectedfrom">(Redirected from <a href="/w/index.php?title=Signaling_protein&redirect=no" class="mw-redirect" title="Signaling protein">Signaling protein</a>)</span></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">System of communication</div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">For the journal, see <a href="/wiki/Cellular_Signalling" title="Cellular Signalling">Cellular Signalling</a>.</div> <p>In <a href="/wiki/Biology" title="Biology">biology</a>, <b>cell signaling</b> (<b>cell signalling</b> in <a href="/wiki/British_English" title="British English">British English</a>) is the <a href="/wiki/Biological_process" title="Biological process">process</a> by which a <a href="/wiki/Cell_(biology)" title="Cell (biology)">cell</a> interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all <a href="/wiki/Cell_(biology)" title="Cell (biology)">cellular life</a> in <a href="/wiki/Prokaryote" title="Prokaryote">prokaryotes</a> and <a href="/wiki/Eukaryote" title="Eukaryote">eukaryotes</a>. </p><p>Typically, the signaling process involves three components: the signal, the receptor, and the effector.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (January 2024)">citation needed</span></a></i>]</sup> </p><p>In biology, signals are mostly chemical in nature, but can also be physical cues such as <a href="/wiki/Pressure" title="Pressure">pressure</a>, <a href="/wiki/Membrane_potential" title="Membrane potential">voltage</a>, <a href="/wiki/Temperature" title="Temperature">temperature</a>, or light. Chemical signals are molecules with the ability to bind and activate a specific <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a>. These molecules, also referred as ligands, are chemically diverse, including <a href="/wiki/Ion" title="Ion">ions</a> (e.g. Na+, K+, Ca++, etc.), lipids (e.g. steroid, prostaglandin), peptides (e.g. insulin, ACTH), carbohydrates, glycosylated proteins (proteoglycans), nucleic acids, etc. Peptide and lipid ligands are particularly important, as most hormones belong to these classes of chemicals. Peptides are usually polar, hydrophilic molecules. As such they are unable to diffuse freely across the bi-lipid layer of the plasma membrane, so their action is mediated by a cell membrane bound receptor. On the other hand, liposoluble chemicals such as steroid hormones, can diffuse passively across the plasma membrane and interact with intracellular receptors. Cell signaling can occur over short or long distances, and can be further classified as <a href="/wiki/Autocrine" class="mw-redirect" title="Autocrine">autocrine</a>, <a href="/wiki/Intracrine" title="Intracrine">intracrine</a>, <a href="/wiki/Juxtacrine" class="mw-redirect" title="Juxtacrine">juxtacrine</a>, <a href="/wiki/Paracrine" class="mw-redirect" title="Paracrine">paracrine</a>, or <a href="/wiki/Endocrine" class="mw-redirect" title="Endocrine">endocrine</a>. <a href="/wiki/Autocrine_signaling" title="Autocrine signaling">Autocrine signaling</a> occurs when the chemical signal acts on the same cell that produced the signaling chemical.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Intracrine signaling occurs when the chemical signal produced by a cell acts on receptors located in the cytoplasm or nucleus of the same cell.<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> Juxtacrine signaling occurs between physically adjacent cells.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Paracrine signaling occurs between nearby cells. Endocrine interaction occurs between distant cells, with the chemical signal usually carried by the blood.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptors</a> are complex proteins or tightly bound multimer of proteins, located in the plasma membrane or within the interior of the cell such as in the <a href="/wiki/Cytoplasm" title="Cytoplasm">cytoplasm</a>, <a href="/wiki/Organelle" title="Organelle">organelles</a>, and <a href="/wiki/Cell_nucleus" title="Cell nucleus">nucleus</a>. Receptors have the ability to detect a signal either by binding to a specific chemical or by undergoing a conformational change when interacting with physical agents. It is the specificity of the chemical interaction between a given ligand and its receptor that confers the ability to trigger a specific cellular response. Receptors can be broadly classified into cell membrane receptors and intracellular receptors. </p><p><a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">Cell membrane receptors</a> can be further classified into ion channel linked receptors, G-Protein coupled receptors and enzyme linked receptors. </p><p>Ion channels receptors are large transmembrane proteins with a ligand activated gate function. When these receptors are activated, they may allow or block passage of specific ions across the cell membrane. Most receptors activated by physical stimuli such as pressure or temperature belongs to this category. </p><p><a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">G-protein receptors</a> are multimeric proteins embedded within the plasma membrane. These receptors have extracellular, trans-membrane and intracellular domains. The extracellular domain is responsible for the interaction with a specific ligand. The intracellular domain is responsible for the initiation of a cascade of chemical reactions which ultimately triggers the specific cellular function controlled by the receptor. </p><p><a href="/wiki/Enzyme-linked_receptor" title="Enzyme-linked receptor">Enzyme-linked receptors</a> are <a href="/wiki/Transmembrane_protein" title="Transmembrane protein">transmembrane proteins</a> with an extracellular domain responsible for binding a specific ligand and an intracellular domain with enzymatic or catalytic activity. Upon activation the enzymatic portion is responsible for promoting specific intracellular chemical reactions. </p><p><a href="/wiki/Intracellular_receptor" title="Intracellular receptor">Intracellular receptors</a> have a different mechanism of action. They usually bind to lipid soluble ligands that diffuse passively through the plasma membrane such as steroid hormones. These ligands bind to specific cytoplasmic transporters that shuttle the hormone-transporter complex inside the nucleus where specific genes are activated and the synthesis of specific proteins is promoted. </p><p>The effector component of the signaling pathway begins with <a href="/wiki/Signal_transduction" title="Signal transduction">signal transduction</a>. In this process, the signal, by interacting with the receptor, starts a series of molecular events within the cell leading to the final effect of the signaling process. Typically the final effect consists in the activation of an ion channel (<a href="/wiki/Ligand-gated_ion_channel" title="Ligand-gated ion channel">ligand-gated ion channel</a>) or the initiation of a <a href="/wiki/Second_messenger_system" title="Second messenger system">second messenger system</a> cascade that propagates the signal through the cell. Second messenger systems can amplify or modulate a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). The <a href="/wiki/Upstream_and_downstream_(transduction)" title="Upstream and downstream (transduction)">downstream effects</a> of these signaling pathways may include additional enzymatic activities such as <a href="/wiki/Protease" title="Protease">proteolytic cleavage</a>, <a href="/wiki/Phosphorylation" title="Phosphorylation">phosphorylation</a>, <a href="/wiki/Methylation" title="Methylation">methylation</a>, and <a href="/wiki/Ubiquitinylation" class="mw-redirect" title="Ubiquitinylation">ubiquitinylation</a>. </p><p>Signaling molecules can be synthesized from various biosynthetic pathways and released through <a href="/wiki/Passive_transport" title="Passive transport">passive</a> or <a href="/wiki/Active_transport" title="Active transport">active transports</a>, or even from <a href="/wiki/Cell_damage" title="Cell damage">cell damage</a>. </p><p>Each cell is programmed to respond to specific extracellular signal molecules, and is the basis of <a href="/wiki/Developmental_biology" title="Developmental biology">development</a>, <a href="/wiki/Tissue_repair" class="mw-redirect" title="Tissue repair">tissue repair</a>, <a href="/wiki/Immunity_(medical)" class="mw-redirect" title="Immunity (medical)">immunity</a>, and <a href="/wiki/Homeostasis" title="Homeostasis">homeostasis</a>. Errors in signaling interactions may cause diseases such as <a href="/wiki/Cancer" title="Cancer">cancer</a>, <a href="/wiki/Autoimmunity" title="Autoimmunity">autoimmunity</a>, and <a href="/wiki/Diabetes" title="Diabetes">diabetes</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Taxonomic_range">Taxonomic range</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=1" title="Edit section: Taxonomic range"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In many small organisms such as <a href="/wiki/Bacteria" title="Bacteria">bacteria</a>, <a href="/wiki/Quorum_sensing" title="Quorum sensing">quorum sensing</a> enables individuals to begin an activity only when the population is sufficiently large. This signaling between cells was first observed in the marine bacterium <i><a href="/wiki/Aliivibrio_fischeri" title="Aliivibrio fischeri">Aliivibrio fischeri</a></i>, which <a href="/wiki/Bioluminescence" title="Bioluminescence">produces light</a> when the population is dense enough.<sup id="cite_ref-Nealson-et-al-1970_5-0" class="reference"><a href="#cite_note-Nealson-et-al-1970-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> The mechanism involves the production and detection of a signaling molecule, and the regulation of gene transcription in response. Quorum sensing operates in both gram-positive and gram-negative bacteria, and both within and between species.<sup id="cite_ref-Bassler-1999_6-0" class="reference"><a href="#cite_note-Bassler-1999-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>In <a href="/wiki/Slime_mold" title="Slime mold">slime molds</a>, individual cells aggregate together to form fruiting bodies and eventually spores, under the influence of a chemical signal, known as an <a href="/wiki/Acrasin" title="Acrasin">acrasin</a>. The individuals move by <a href="/wiki/Chemotaxis" title="Chemotaxis">chemotaxis</a>, i.e. they are attracted by the chemical gradient. Some species use <a href="/wiki/Cyclic_AMP" class="mw-redirect" title="Cyclic AMP">cyclic AMP</a> as the signal; others such as <i><a href="/wiki/Polysphondylium_violaceum" class="mw-redirect" title="Polysphondylium violaceum">Polysphondylium violaceum</a></i> use a <a href="/wiki/Dipeptide" title="Dipeptide">dipeptide</a> known as <a href="/wiki/Dipeptide#Other_dipeptides" title="Dipeptide">glorin</a>.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p><p>In plants and animals, signaling between cells occurs either through release into the <a href="/wiki/Extracellular_space" title="Extracellular space">extracellular space</a>, divided in <a href="/wiki/Paracrine_signaling" title="Paracrine signaling">paracrine signaling</a> (over short distances) and <a href="/wiki/Endocrine_signaling" class="mw-redirect" title="Endocrine signaling">endocrine signaling</a> (over long distances), or by direct contact, known as <a href="/wiki/Juxtacrine_signaling" class="mw-redirect" title="Juxtacrine signaling">juxtacrine signaling</a> such as <a href="/wiki/Notch_signaling" class="mw-redirect" title="Notch signaling">notch signaling</a>.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Autocrine_signaling" title="Autocrine signaling">Autocrine signaling</a> is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule.<sup id="cite_ref-bruce_9-0" class="reference"><a href="#cite_note-bruce-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Synapse" title="Synapse">Synaptic</a> signaling is a special case of paracrine signaling (for <a href="/wiki/Chemical_synapse" title="Chemical synapse">chemical synapses</a>) or juxtacrine signaling (for <a href="/wiki/Electrical_synapse" title="Electrical synapse">electrical synapses</a>) between <a href="/wiki/Neuron" title="Neuron">neurons</a> and target cells. </p> <div class="mw-heading mw-heading2"><h2 id="Extracellular_signal">Extracellular signal</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=2" title="Edit section: Extracellular signal"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Synthesis_and_release">Synthesis and release</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=3" title="Edit section: Synthesis and release"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Cell_signalling.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a4/Cell_signalling.png/350px-Cell_signalling.png" decoding="async" width="350" height="162" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a4/Cell_signalling.png/525px-Cell_signalling.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a4/Cell_signalling.png/700px-Cell_signalling.png 2x" data-file-width="897" data-file-height="416" /></a><figcaption>Different types of extracellular signaling</figcaption></figure> <p>Many cell signals are carried by molecules that are released by one cell and move to make contact with another cell. Signaling molecules can belong to several chemical classes: <a href="/wiki/Lipid" title="Lipid">lipids</a>, <a href="/wiki/Phospholipid" title="Phospholipid">phospholipids</a>, <a href="/wiki/Amino_acid" title="Amino acid">amino acids</a>, <a href="/wiki/Monoamine" class="mw-redirect" title="Monoamine">monoamines</a>, <a href="/wiki/Protein" title="Protein">proteins</a>, <a href="/wiki/Glycoprotein" title="Glycoprotein">glycoproteins</a>, or <a href="/wiki/Gaseous_signaling_molecules" title="Gaseous signaling molecules">gases</a>. Signaling molecules binding surface receptors are generally large and <a href="/wiki/Hydrophilic" class="mw-redirect" title="Hydrophilic">hydrophilic</a> (e.g. <a href="/wiki/TRH" class="mw-redirect" title="TRH">TRH</a>, <a href="/wiki/Vasopressin" title="Vasopressin">Vasopressin</a>, <a href="/wiki/Acetylcholine" title="Acetylcholine">Acetylcholine</a>), while those entering the cell are generally small and <a href="/wiki/Hydrophobic" class="mw-redirect" title="Hydrophobic">hydrophobic</a> (e.g. <a href="/wiki/Glucocorticoid" title="Glucocorticoid">glucocorticoids</a>, <a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">thyroid hormones</a>, <a href="/wiki/Cholecalciferol" title="Cholecalciferol">cholecalciferol</a>, <a href="/wiki/Retinoic_acid" title="Retinoic acid">retinoic acid</a>), but important exceptions to both are numerous, and the same molecule can act both via surface receptors or in an intracrine manner to different effects.<sup id="cite_ref-bruce_9-1" class="reference"><a href="#cite_note-bruce-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> In animal cells, specialized cells release these hormones and send them through the circulatory system to other parts of the body. They then reach target cells, which can recognize and respond to the hormones and produce a result. This is also known as endocrine signaling. Plant growth regulators, or plant hormones, move through cells or by diffusing through the air as a gas to reach their targets.<sup id="cite_ref-Reece_10-0" class="reference"><a href="#cite_note-Reece-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Hydrogen_sulfide#Function_in_the_body" title="Hydrogen sulfide">Hydrogen sulfide</a> is produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in the human body: <a href="/wiki/Biological_functions_of_nitric_oxide" title="Biological functions of nitric oxide">nitric oxide</a> and <a href="/wiki/Carbon_monoxide#Physiology" title="Carbon monoxide">carbon monoxide</a>.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Exocytosis">Exocytosis</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=4" title="Edit section: Exocytosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Exocytosis" title="Exocytosis">Exocytosis</a> is the process by which a cell transports <a href="/wiki/Molecule" title="Molecule">molecules</a> such as <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a> and <a href="/wiki/Protein" title="Protein">proteins</a> out of the cell. As an <a href="/wiki/Active_transport" title="Active transport">active transport</a> mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, <a href="/wiki/Endocytosis" title="Endocytosis">endocytosis</a>, the process that brings substances into the cell, are used by all cells because most <a href="/wiki/Chemical_substance" title="Chemical substance">chemical substances</a> important to them are large <a href="/wiki/Chemical_polarity" title="Chemical polarity">polar</a> molecules that cannot pass through the <a href="/wiki/Hydrophobic" class="mw-redirect" title="Hydrophobic">hydrophobic</a> portion of the <a href="/wiki/Cell_membrane" title="Cell membrane">cell membrane</a> by <a href="/wiki/Passive_transport" title="Passive transport">passive transport</a>. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called <a href="/wiki/Porosome" title="Porosome">porosomes</a>. Porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>In exocytosis, membrane-bound secretory <a href="/wiki/Vesicle_(biology)" class="mw-redirect" title="Vesicle (biology)">vesicles</a> are carried to the <a href="/wiki/Cell_membrane" title="Cell membrane">cell membrane</a>, where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. This <a href="/wiki/Secretion" title="Secretion">secretion</a> is possible because the vesicle transiently <a href="/wiki/Vesicle_fusion" title="Vesicle fusion">fuses</a> with the plasma membrane. In the context of <a href="/wiki/Neurotransmission" title="Neurotransmission">neurotransmission</a>, neurotransmitters are typically released from <a href="/wiki/Synaptic_vesicle" title="Synaptic vesicle">synaptic vesicles</a> into the <a href="/wiki/Synaptic_cleft" class="mw-redirect" title="Synaptic cleft">synaptic cleft</a> via exocytosis; however, neurotransmitters can also be released via <a href="/wiki/Reverse_transport" title="Reverse transport">reverse transport</a> through <a href="/wiki/Membrane_transport_protein" title="Membrane transport protein">membrane transport proteins</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (September 2023)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading3"><h3 id="Forms_of_Cell_Signaling">Forms of Cell Signaling</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=5" title="Edit section: Forms of Cell Signaling"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading4"><h4 id="Autocrine">Autocrine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=6" title="Edit section: Autocrine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Autocrine_and_Paracrine.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/5e/Autocrine_and_Paracrine.png/350px-Autocrine_and_Paracrine.png" decoding="async" width="350" height="195" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/5e/Autocrine_and_Paracrine.png/525px-Autocrine_and_Paracrine.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/5e/Autocrine_and_Paracrine.png/700px-Autocrine_and_Paracrine.png 2x" data-file-width="752" data-file-height="419" /></a><figcaption>Differences between autocrine and paracrine signaling</figcaption></figure> <p>Autocrine signaling involves a cell secreting a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell itself.<sup id="cite_ref-one_13-0" class="reference"><a href="#cite_note-one-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> This can be contrasted with <a href="/wiki/Paracrine_signaling" title="Paracrine signaling">paracrine signaling</a>, <a href="/wiki/Intracrine" title="Intracrine">intracrine</a> signaling, or classical <a href="/wiki/Endocrine" class="mw-redirect" title="Endocrine">endocrine</a> signaling. </p> <div class="mw-heading mw-heading4"><h4 id="Intracrine">Intracrine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=7" title="Edit section: Intracrine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In intracrine signaling, the signaling chemicals are produced inside the cell and bind to cytosolic or nuclear receptors without being secreted from the cell.. In intracrine signaling, signals are relayed without being secreted from the cell. The intracrine signals not being secreted outside of the cell is what sets apart intracrine signaling from the other cell signaling mechanisms such as autocrine signaling. In both autocrine and intracrine signaling, the signal has an effect on the cell that produced it.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Juxtacrine">Juxtacrine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=8" title="Edit section: Juxtacrine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Juxtacrine signaling is a type of <a href="/wiki/Cell_(biology)" title="Cell (biology)">cell</a>–cell or cell–<a href="/wiki/Extracellular_matrix" title="Extracellular matrix">extracellular matrix</a> signaling in <a href="/wiki/Multicellular" class="mw-redirect" title="Multicellular">multicellular</a> organisms that requires close contact. There are three types: </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Forms_of_Cell_Signaling.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/b9/Forms_of_Cell_Signaling.png/220px-Forms_of_Cell_Signaling.png" decoding="async" width="220" height="265" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/b9/Forms_of_Cell_Signaling.png/330px-Forms_of_Cell_Signaling.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/b9/Forms_of_Cell_Signaling.png/440px-Forms_of_Cell_Signaling.png 2x" data-file-width="1080" data-file-height="1300" /></a><figcaption>This image displays the different types of cell signaling</figcaption></figure> <ol><li>A membrane <a href="/wiki/Ligand" title="Ligand">ligand</a> (<a href="/wiki/Protein" title="Protein">protein</a>, <a href="/wiki/Oligosaccharide" title="Oligosaccharide">oligosaccharide</a>, <a href="/wiki/Lipid" title="Lipid">lipid</a>) and a <a href="/wiki/Membrane_protein" title="Membrane protein">membrane protein</a> of two adjacent cells <a href="/wiki/Protein_interaction" class="mw-redirect" title="Protein interaction">interact</a>.</li> <li>A communicating <a href="/wiki/Cell_junction" title="Cell junction">junction</a> links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules.</li> <li>An <a href="/wiki/Extracellular_matrix" title="Extracellular matrix">extracellular matrix</a> <a href="/wiki/Glycoprotein" title="Glycoprotein">glycoprotein</a> and a membrane protein interact.</li></ol> <p>Additionally, in <a href="/wiki/Unicellular" class="mw-redirect" title="Unicellular">unicellular</a> organisms such as <a href="/wiki/Bacteria" title="Bacteria">bacteria</a>, juxtacrine signaling means interactions by membrane contact. Juxtacrine signaling has been observed for some <a href="/wiki/Growth_factor" title="Growth factor">growth factors</a>, <a href="/wiki/Cytokine" title="Cytokine">cytokine</a> and <a href="/wiki/Chemokine" title="Chemokine">chemokine</a> cellular signals, playing an important role in the <a href="/wiki/Immune_response" title="Immune response">immune response</a>. Juxtacrine signalling via direct membrane contacts is also present between neuronal cell bodies and motile processes of <a href="/wiki/Microglia" title="Microglia">microglia</a> both during development,<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> and in the adult brain.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Paracrine">Paracrine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=9" title="Edit section: Paracrine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In paracrine signaling, a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by <a href="/wiki/Endocrine_system" title="Endocrine system">endocrine factors</a>, hormones which travel considerably longer distances via the <a href="/wiki/Circulatory_system" title="Circulatory system">circulatory system</a>; <a href="/wiki/Juxtacrine_signaling" class="mw-redirect" title="Juxtacrine signaling">juxtacrine interactions</a>; and <a href="/wiki/Autocrine_signaling" title="Autocrine signaling">autocrine signaling</a>. Cells that produce paracrine factors secrete them into the immediate <a href="/wiki/Extracellular" class="mw-redirect" title="Extracellular">extracellular</a> environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain. </p><p><a href="/wiki/Paracrine_signalling" class="mw-redirect" title="Paracrine signalling">Paracrine</a> signals such as <a href="/wiki/Retinoic_acid" title="Retinoic acid">retinoic acid</a> target only cells in the vicinity of the emitting cell.<sup id="cite_ref-Duester_17-0" class="reference"><a href="#cite_note-Duester-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Neurotransmitter" title="Neurotransmitter">Neurotransmitters</a> represent another example of a paracrine signal. </p><p>Some signaling molecules can function as both a hormone and a neurotransmitter. For example, <a href="/wiki/Epinephrine" class="mw-redirect" title="Epinephrine">epinephrine</a> and <a href="/wiki/Norepinephrine" title="Norepinephrine">norepinephrine</a> can function as hormones when released from the <a href="/wiki/Adrenal_gland" title="Adrenal gland">adrenal gland</a> and are transported to the heart by way of the blood stream. Norepinephrine can also be produced by <a href="/wiki/Neuron" title="Neuron">neurons</a> to function as a neurotransmitter within the brain.<sup id="cite_ref-Cartford2004_18-0" class="reference"><a href="#cite_note-Cartford2004-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Estrogen" title="Estrogen">Estrogen</a> can be released by the <a href="/wiki/Ovary" title="Ovary">ovary</a> and function as a hormone or act locally via paracrine or <a href="/wiki/Autocrine" class="mw-redirect" title="Autocrine">autocrine</a> signaling.<sup id="cite_ref-Jesmin2004_19-0" class="reference"><a href="#cite_note-Jesmin2004-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptors</a> and pathways. In fact, different <a href="/wiki/Organ_(biology)" title="Organ (biology)">organs</a> in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> The highly conserved receptors and pathways can be organized into four major families based on similar structures: <a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">fibroblast growth factor</a> (FGF) family, <a href="/wiki/Hedgehog_signaling_pathway" title="Hedgehog signaling pathway">Hedgehog</a> family, <a href="/wiki/Wnt_signaling_pathway" title="Wnt signaling pathway">Wnt</a> family, and <a href="/wiki/Transforming_growth_factor_beta" title="Transforming growth factor beta">TGF-β superfamily</a>. Binding of a paracrine factor to its respective receptor initiates <a href="/wiki/Signal_transduction" title="Signal transduction">signal transduction</a> cascades, eliciting different responses. </p> <div class="mw-heading mw-heading4"><h4 id="Endocrine">Endocrine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=10" title="Edit section: Endocrine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i><a href="/wiki/Endocrine_system" title="Endocrine system">Endocrine</a></i> signals are called <a href="/wiki/Hormone" title="Hormone">hormones</a>. Hormones are produced by endocrine cells and they travel through the <a href="/wiki/Circulatory_system" title="Circulatory system">blood</a> to reach all parts of the body. Specificity of signaling can be controlled if only some cells can respond to a particular hormone. Endocrine signaling involves the release of <a href="/wiki/Hormone" title="Hormone">hormones</a> by internal <a href="/wiki/Gland" title="Gland">glands</a> of an <a href="/wiki/Organism" title="Organism">organism</a> directly into the <a href="/wiki/Circulatory_system" title="Circulatory system">circulatory system</a>, regulating distant target organs. In <a href="/wiki/Vertebrate" title="Vertebrate">vertebrates</a>, the <a href="/wiki/Hypothalamus" title="Hypothalamus">hypothalamus</a> is the neural control center for all endocrine systems. In <a href="/wiki/Humans" class="mw-redirect" title="Humans">humans</a>, the major <a href="/wiki/Endocrine_gland" title="Endocrine gland">endocrine glands</a> are the <a href="/wiki/Thyroid_gland" class="mw-redirect" title="Thyroid gland">thyroid gland</a> and the <a href="/wiki/Adrenal_gland" title="Adrenal gland">adrenal glands</a>. The study of the endocrine system and its disorders is known as <a href="/wiki/Endocrinology" title="Endocrinology">endocrinology</a>. </p> <div class="mw-heading mw-heading2"><h2 id="Receptors">Receptors</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=11" title="Edit section: Receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptor (biochemistry)</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Ligand-receptor_interaction.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/13/Ligand-receptor_interaction.png/350px-Ligand-receptor_interaction.png" decoding="async" width="350" height="152" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/13/Ligand-receptor_interaction.png/525px-Ligand-receptor_interaction.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/13/Ligand-receptor_interaction.png/700px-Ligand-receptor_interaction.png 2x" data-file-width="2756" data-file-height="1200" /></a><figcaption>Transmembrane receptor working principle</figcaption></figure> <p>Cells receive information from their neighbors through a class of proteins known as <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptors</a>. Receptors may bind with some molecules (ligands) or may interact with physical agents like light, mechanical temperature, pressure, etc. Reception occurs when the target cell (any cell with a <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor protein</a> specific to the <a href="/wiki/Signal_molecule" class="mw-redirect" title="Signal molecule">signal molecule</a>) detects a signal, usually in the form of a small, water-soluble molecule, via binding to a receptor protein on the cell surface, or once inside the cell, the signaling molecule can bind to <a href="/wiki/Intracellular_receptor" title="Intracellular receptor">intracellular receptors</a>, other elements, or stimulate <a href="/wiki/Enzyme" title="Enzyme">enzyme</a> activity (e.g. gasses), as in intracrine signaling. </p><p>Signaling molecules interact with a target cell as a <a href="/wiki/Ligand" title="Ligand">ligand</a> to <a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">cell surface receptors</a>, and/or by entering into the cell through its <a href="/wiki/Cell_membrane" title="Cell membrane">membrane</a> or <a href="/wiki/Endocytosis" title="Endocytosis">endocytosis</a> for <a href="/wiki/Intracrine" title="Intracrine">intracrine</a> signaling. This generally results in the activation of <a href="/wiki/Second_messenger" class="mw-redirect" title="Second messenger">second messengers</a>, leading to various physiological effects. In many mammals, early <a href="/wiki/Embryo" title="Embryo">embryo</a> cells exchange signals with cells of the <a href="/wiki/Uterus" title="Uterus">uterus</a>.<sup id="cite_ref-Mohamed2005_21-0" class="reference"><a href="#cite_note-Mohamed2005-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> In the human <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal tract</a>, <a href="/wiki/Bacteria" title="Bacteria">bacteria</a> exchange signals with each other and with human <a href="/wiki/Epithelium" title="Epithelium">epithelial</a> and <a href="/wiki/Immune_system" title="Immune system">immune system</a> cells.<sup id="cite_ref-Clarke2005_22-0" class="reference"><a href="#cite_note-Clarke2005-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> For the yeast <i><a href="/wiki/Saccharomyces_cerevisiae" title="Saccharomyces cerevisiae">Saccharomyces cerevisiae</a></i> during <a href="/wiki/Mating_of_yeast" title="Mating of yeast">mating</a>, some cells send a <a href="/wiki/Peptide" title="Peptide">peptide</a> signal (mating factor <a href="/wiki/Pheromone" title="Pheromone">pheromones</a>) into their environment. The mating factor peptide may bind to a cell surface <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a> on other yeast cells and induce them to prepare for mating.<sup id="cite_ref-Lin2004_23-0" class="reference"><a href="#cite_note-Lin2004-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Cell_surface_receptors">Cell surface receptors</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=12" title="Edit section: Cell surface receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">Ligand (biochemistry)</a> and <a href="/wiki/Receptor%E2%80%93ligand_kinetics" title="Receptor–ligand kinetics">Receptor–ligand kinetics</a></div> <p>Cell surface receptors play an essential role in the biological systems of single- and multi-cellular organisms and malfunction or damage to these proteins is associated with cancer, heart disease, and asthma.<sup id="cite_ref-pmid17607357_24-0" class="reference"><a href="#cite_note-pmid17607357-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> These <a href="/wiki/Transmembrane_protein" title="Transmembrane protein">trans-membrane</a> receptors are able to transmit information from outside the cell to the inside because they <a href="/wiki/Conformational_change" title="Conformational change">change conformation</a> when a specific ligand binds to it. There are three major types: <a href="/wiki/Ligand-gated_ion_channels" class="mw-redirect" title="Ligand-gated ion channels">Ion channel linked receptors</a>, <a href="/wiki/G_protein%E2%80%93coupled_receptor" class="mw-redirect" title="G protein–coupled receptor">G protein–coupled receptors</a>, and <a href="/wiki/Enzyme-linked_receptor" title="Enzyme-linked receptor">enzyme-linked receptors</a>. </p> <div class="mw-heading mw-heading4"><h4 id="Ion_channel_linked_receptors">Ion channel linked receptors</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=13" title="Edit section: Ion channel linked receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:AMPA_receptor.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/56/AMPA_receptor.png/220px-AMPA_receptor.png" decoding="async" width="220" height="215" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/56/AMPA_receptor.png/330px-AMPA_receptor.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/56/AMPA_receptor.png/440px-AMPA_receptor.png 2x" data-file-width="2078" data-file-height="2034" /></a><figcaption>The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2</figcaption></figure> <p>Ion channel linked receptors are a group of <a href="/wiki/Transmembrane" class="mw-redirect" title="Transmembrane">transmembrane</a> <a href="/wiki/Ion-channel" class="mw-redirect" title="Ion-channel">ion-channel</a> proteins which open to allow ions such as <a href="/wiki/Sodium" title="Sodium">Na<sup>+</sup></a>, <a href="/wiki/Potassium" title="Potassium">K<sup>+</sup></a>, <a href="/wiki/Calcium" title="Calcium">Ca<sup>2+</sup></a>, and/or <a href="/wiki/Chloride" title="Chloride">Cl<sup>−</sup></a> to pass through the membrane in response to the binding of a chemical messenger (i.e. a <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligand</a>), such as a <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a>.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Purves_27-0" class="reference"><a href="#cite_note-Purves-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p><p>When a <a href="/wiki/Presynaptic_neuron" class="mw-redirect" title="Presynaptic neuron">presynaptic neuron</a> is excited, it releases a <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> from vesicles into the <a href="/wiki/Synaptic_cleft" class="mw-redirect" title="Synaptic cleft">synaptic cleft</a>. The neurotransmitter then binds to receptors located on the <a href="/wiki/Postsynaptic_neuron" class="mw-redirect" title="Postsynaptic neuron">postsynaptic neuron</a>. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a <a href="/wiki/Depolarization" title="Depolarization">depolarization</a>, for an excitatory receptor response, or a <a href="/wiki/Hyperpolarization_(biology)" title="Hyperpolarization (biology)">hyperpolarization</a>, for an inhibitory response. </p><p>These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an <a href="/wiki/Allosteric_regulation" title="Allosteric regulation">allosteric</a> binding site). This modularity has enabled a 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located at <a href="/wiki/Synapse" title="Synapse">synapses</a> is to convert the chemical signal of <a href="/wiki/Presynaptic" class="mw-redirect" title="Presynaptic">presynaptically</a> released neurotransmitter directly and very quickly into a <a href="/wiki/Postsynaptic" class="mw-redirect" title="Postsynaptic">postsynaptic</a> electrical signal. Many LICs are additionally modulated by <a href="/wiki/Allosteric" class="mw-redirect" title="Allosteric">allosteric</a> <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a>, by <a href="/wiki/Channel_blockers" class="mw-redirect" title="Channel blockers">channel blockers</a>, <a href="/wiki/Ion" title="Ion">ions</a>, or the <a href="/wiki/Membrane_potential" title="Membrane potential">membrane potential</a>. LICs are classified into three superfamilies which lack evolutionary relationship: <a href="/wiki/Cys-loop_receptor" title="Cys-loop receptor">cys-loop receptors</a>, <a href="/wiki/Glutamate-gated_ion_channel_family" class="mw-redirect" title="Glutamate-gated ion channel family">ionotropic glutamate receptors</a> and <a href="/wiki/P2X_purinoreceptor" title="P2X purinoreceptor">ATP-gated channels</a>. </p> <div class="mw-heading mw-heading4"><h4 id="G_protein–coupled_receptors"><span id="G_protein.E2.80.93coupled_receptors"></span>G protein–coupled receptors</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=14" title="Edit section: G protein–coupled receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:PDB_1hzx_7TM_Sketch_Membrane.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f5/PDB_1hzx_7TM_Sketch_Membrane.png/220px-PDB_1hzx_7TM_Sketch_Membrane.png" decoding="async" width="220" height="154" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f5/PDB_1hzx_7TM_Sketch_Membrane.png/330px-PDB_1hzx_7TM_Sketch_Membrane.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f5/PDB_1hzx_7TM_Sketch_Membrane.png/440px-PDB_1hzx_7TM_Sketch_Membrane.png 2x" data-file-width="1029" data-file-height="720" /></a><figcaption>A G Protein-coupled receptor within the plasma membrane</figcaption></figure> <p>G protein-coupled receptors are a large group of <a href="/wiki/Protein_family" title="Protein family">evolutionarily-related proteins</a> that are <a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">cell surface receptors</a> that detect <a href="/wiki/Molecule" title="Molecule">molecules</a> outside the <a href="/wiki/Cell_(biology)" title="Cell (biology)">cell</a> and activate cellular responses. Coupling with <a href="/wiki/G_protein" title="G protein">G proteins</a>, they are called seven-transmembrane receptors because they pass through the <a href="/wiki/Cell_membrane" title="Cell membrane">cell membrane</a> seven times. The G-protein acts as a "middle man" transferring the signal from its activated receptor to its target and therefore indirectly regulates that target protein.<sup id="cite_ref-trz_28-0" class="reference"><a href="#cite_note-trz-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by <a href="/wiki/Agonist" title="Agonist">agonists</a> although a spontaneous auto-activation of an empty receptor can also be observed.<sup id="cite_ref-trz_28-1" class="reference"><a href="#cite_note-trz-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p><p>G protein-coupled receptors are found only in <a href="/wiki/Eukaryote" title="Eukaryote">eukaryotes</a>, including <a href="/wiki/Yeast" title="Yeast">yeast</a>, <a href="/wiki/Choanoflagellate" title="Choanoflagellate">choanoflagellates</a>,<sup id="cite_ref-pmid12869759_29-0" class="reference"><a href="#cite_note-pmid12869759-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> and animals. The <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a> that bind and activate these receptors include light-sensitive compounds, <a href="/wiki/Odor" title="Odor">odors</a>, <a href="/wiki/Pheromone" title="Pheromone">pheromones</a>, <a href="/wiki/Hormone" title="Hormone">hormones</a>, and <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a>, and vary in size from small molecules to <a href="/wiki/Peptide" title="Peptide">peptides</a> to large <a href="/wiki/Protein" title="Protein">proteins</a>. G protein-coupled receptors are involved in many diseases. </p><p>There are two principal signal transduction pathways involving the G protein-coupled receptors: <a href="/wiki/Cyclic_adenosine_monophosphate" title="Cyclic adenosine monophosphate">cAMP</a> signal pathway and <a href="/wiki/Phosphatidylinositol" title="Phosphatidylinositol">phosphatidylinositol</a> signal pathway.<sup id="cite_ref-Gilman_1987_30-0" class="reference"><a href="#cite_note-Gilman_1987-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a <a href="/wiki/Guanine_nucleotide_exchange_factor" title="Guanine nucleotide exchange factor">guanine nucleotide exchange factor</a> (GEF). The GPCR can then activate an associated <a href="/wiki/G_protein" title="G protein">G protein</a> by exchanging the <a href="/wiki/Guanosine_diphosphate" title="Guanosine diphosphate">GDP</a> bound to the G protein for a <a href="/wiki/Guanosine_triphosphate" title="Guanosine triphosphate">GTP</a>. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (<a href="/wiki/Gs_alpha_subunit" title="Gs alpha subunit">G<sub>αs</sub></a>, <a href="/wiki/Gi_alpha_subunit" title="Gi alpha subunit">G<sub>αi/o</sub></a>, <a href="/wiki/Gq_alpha_subunit" title="Gq alpha subunit">G<sub>αq/11</sub></a>, <a href="/wiki/G12/G13_alpha_subunits" title="G12/G13 alpha subunits">G<sub>α12/13</sub></a>).<sup id="cite_ref-Wettschureck_2005_31-0" class="reference"><a href="#cite_note-Wettschureck_2005-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 1160">: 1160 </span></sup> </p><p>G protein-coupled receptors are an important drug target and approximately 34%<sup id="cite_ref-Hauser_2018_32-0" class="reference"><a href="#cite_note-Hauser_2018-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018<sup class="plainlinks noexcerpt noprint asof-tag update" style="display:none;"><a class="external text" href="https://en.wikipedia.org/w/index.php?title=Cell_signaling&action=edit">[update]</a></sup>.<sup id="cite_ref-Hauser_2018_32-1" class="reference"><a href="#cite_note-Hauser_2018-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of pharmaceutical research.<sup id="cite_ref-trz_28-2" class="reference"><a href="#cite_note-trz-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Enzyme-linked_receptors">Enzyme-linked receptors</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=15" title="Edit section: Enzyme-linked receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:VEGF_receptors.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c8/VEGF_receptors.png/220px-VEGF_receptors.png" decoding="async" width="220" height="207" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/c8/VEGF_receptors.png/330px-VEGF_receptors.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/c8/VEGF_receptors.png/440px-VEGF_receptors.png 2x" data-file-width="561" data-file-height="528" /></a><figcaption> VEGF receptors are a type of enzyme-coupled receptors, specifically tyrosine kinase receptors</figcaption></figure> <p>Enzyme-linked receptors (or catalytic receptors) are <a href="/wiki/Transmembrane_receptors" class="mw-redirect" title="Transmembrane receptors">transmembrane receptors</a> that, upon activation by an extracellular <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligand</a>, causes <a href="/wiki/Enzymatic" class="mw-redirect" title="Enzymatic">enzymatic</a> activity on the intracellular side.<sup id="cite_ref-Dudek2006_33-0" class="reference"><a href="#cite_note-Dudek2006-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> Hence a catalytic receptor is an <a href="/wiki/Integral_membrane_protein" title="Integral membrane protein">integral membrane protein</a> possessing both <a href="/wiki/Enzyme" title="Enzyme">enzymatic</a>, <a href="/wiki/Catalysis" title="Catalysis">catalytic</a>, and <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a> functions.<sup id="cite_ref-pmc2013840_34-0" class="reference"><a href="#cite_note-pmc2013840-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p><p>They have two important domains, an extra-cellular ligand binding domain and an intracellular domain, which has a catalytic function; and a single <a href="/wiki/Transmembrane_helix" class="mw-redirect" title="Transmembrane helix">transmembrane helix</a>. The signaling molecule binds to the receptor on the outside of the cell and causes a conformational change on the catalytic function located on the receptor inside the cell.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (September 2023)">citation needed</span></a></i>]</sup> Examples of the enzymatic activity include: </p> <ul><li><a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">Receptor tyrosine kinase</a>, as in <a href="/wiki/Fibroblast_growth_factor_receptor" title="Fibroblast growth factor receptor">fibroblast growth factor receptor</a>. Most enzyme-linked receptors are of this type.<sup id="cite_ref-35" class="reference"><a href="#cite_note-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Serine/threonine-specific_protein_kinase" title="Serine/threonine-specific protein kinase">Serine/threonine-specific protein kinase</a>, as in <a href="/wiki/Bone_morphogenetic_protein" title="Bone morphogenetic protein">bone morphogenetic protein</a></li> <li><a href="/wiki/Guanylate_cyclase" title="Guanylate cyclase">Guanylate cyclase</a>, as in <a href="/wiki/Atrial_natriuretic_factor_receptor" class="mw-redirect" title="Atrial natriuretic factor receptor">atrial natriuretic factor receptor</a></li></ul> <div class="mw-heading mw-heading4"><h4 id="Intracellular_receptors">Intracellular receptors</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=16" title="Edit section: Intracellular receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Intracellular receptors exist freely in the cytoplasm, nucleus, or can be bound to organelles or membranes. For example, the presence of nuclear and mitochondrial receptors is well documented.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> The binding of a ligand to the intracellular receptor typically induces a response in the cell. Intracellular receptors often have a level of specificity, this allows the receptors to initiate certain responses when bound to a corresponding ligand.<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> Intracellular receptors typically act on lipid soluble molecules. The receptors bind to a group of DNA binding proteins. Upon binding, the receptor-ligand complex translocates to the nucleus where they can alter patterns of gene expression.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Steroid_hormone_receptor">Steroid hormone receptor</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=17" title="Edit section: Steroid hormone receptor"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Steroid_hormone_receptor" title="Steroid hormone receptor">Steroid hormone receptor</a></div> <p>Steroid hormone receptors are found in the <a href="/wiki/Cell_nucleus" title="Cell nucleus">nucleus</a>, <a href="/wiki/Cytosol" title="Cytosol">cytosol</a>, and also on the <a href="/wiki/Plasma_membrane" class="mw-redirect" title="Plasma membrane">plasma membrane</a> of target cells. They are generally <a href="/wiki/Intracellular_receptor" title="Intracellular receptor">intracellular receptors</a> (typically cytoplasmic or nuclear) and initiate <a href="/wiki/Signal_transduction" title="Signal transduction">signal transduction</a> for <a href="/wiki/Steroid_hormone" title="Steroid hormone">steroid hormones</a> which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptors</a> are members of the <a href="/wiki/Nuclear_receptor" title="Nuclear receptor">nuclear receptor</a> subfamily 3 (NR3) that include receptors for <a href="/wiki/Estrogen" title="Estrogen">estrogen</a> (group NR3A)<sup id="cite_ref-pmid17132854_39-0" class="reference"><a href="#cite_note-pmid17132854-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> and 3-ketosteroids (group NR3C).<sup id="cite_ref-pmid17132855_40-0" class="reference"><a href="#cite_note-pmid17132855-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> In addition to nuclear receptors, several <a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">G protein-coupled receptors</a> and <a href="/wiki/Ion_channel" title="Ion channel">ion channels</a> act as <a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">cell surface receptors</a> for certain steroid hormones. </p> <div class="mw-heading mw-heading2"><h2 id="Mechanisms_of_Receptor_Down-Regulation">Mechanisms of Receptor Down-Regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=18" title="Edit section: Mechanisms of Receptor Down-Regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Receptor-mediated_endocytosis" title="Receptor-mediated endocytosis">Receptor mediated endocytosis</a> is common way of turning receptors "off". Endocytic down regulation is regarded as a means for reducing receptor signaling.<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> The process involves the binding of a ligand to the receptor, which then triggers the formation of coated pits, the coated pits transform to coated vesicles and are transported to the endosome. </p><p>Receptor Phosphorylation is another type of receptor down-regulation. Biochemical changes can reduce receptor affinity for a ligand.<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> </p><p>Reducing the sensitivity of the receptor is a result of receptors being occupied for a long time. This results in a receptor adaptation in which the receptor no longer responds to the signaling molecule. Many receptors have the ability to change in response to ligand concentration.<sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Signal_transduction_pathways">Signal transduction pathways</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=19" title="Edit section: Signal transduction pathways"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Signal_transduction" title="Signal transduction">Signal transduction</a> and <a href="/wiki/List_of_signalling_pathways" title="List of signalling pathways">List of signalling pathways</a></div> <p>When binding to the signaling molecule, the receptor protein changes in some way and starts the process of transduction, which can occur in a single step or as a series of changes in a sequence of different molecules (called a signal transduction pathway). The molecules that compose these pathways are known as relay molecules. The multistep process of the transduction stage is often composed of the activation of proteins by addition or removal of phosphate groups or even the release of other small molecules or ions that can act as messengers. The amplifying of a signal is one of the benefits to this multiple step sequence. Other benefits include more opportunities for regulation than simpler systems do and the fine-tuning of the response, in both unicellular and multicellular organism.<sup id="cite_ref-Reece_10-1" class="reference"><a href="#cite_note-Reece-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>In some cases, receptor activation caused by ligand binding to a receptor is directly coupled to the cell's response to the ligand. For example, the neurotransmitter <a href="/wiki/Gamma-Aminobutyric_acid" class="mw-redirect" title="Gamma-Aminobutyric acid">GABA</a> can activate a cell surface receptor that is part of an <a href="/wiki/Ion_channel" title="Ion channel">ion channel</a>. GABA binding to a <a href="/wiki/GABAA_receptor" title="GABAA receptor">GABA<sub>A</sub> receptor</a> on a neuron opens a <a href="/wiki/Chloride" title="Chloride">chloride</a>-selective ion channel that is part of the receptor. GABA<sub>A</sub> receptor activation allows negatively charged chloride ions to move into the neuron, which inhibits the ability of the neuron to produce <a href="/wiki/Action_potential" title="Action potential">action potentials</a>. However, for many cell surface receptors, ligand-receptor interactions are not directly linked to the cell's response. The activated receptor must first interact with other proteins inside the cell before the ultimate <a href="/wiki/Physiology" title="Physiology">physiological</a> effect of the ligand on the cell's behavior is produced. Often, the behavior of a chain of several interacting cell proteins is altered following receptor activation. The entire set of cell changes induced by receptor activation is called a <a href="/wiki/Signal_transduction" title="Signal transduction">signal transduction</a> mechanism or pathway.<sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:MAPKpathway_diagram.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/11/MAPKpathway_diagram.svg/220px-MAPKpathway_diagram.svg.png" decoding="async" width="220" height="686" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/11/MAPKpathway_diagram.svg/330px-MAPKpathway_diagram.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/11/MAPKpathway_diagram.svg/440px-MAPKpathway_diagram.svg.png 2x" data-file-width="295" data-file-height="920" /></a><figcaption>Key components of a signal transduction pathway (<a href="/wiki/MAPK/ERK_pathway" title="MAPK/ERK pathway">MAPK/ERK pathway</a> shown)</figcaption></figure> <p>A more complex signal transduction pathway is the MAPK/ERK pathway, which involves changes of <a href="/wiki/Protein%E2%80%93protein_interaction" title="Protein–protein interaction">protein–protein interactions</a> inside the cell, induced by an external signal. Many growth factors bind to receptors at the cell surface and stimulate cells to progress through the <a href="/wiki/Cell_cycle" title="Cell cycle">cell cycle</a> and <a href="/wiki/Cell_division" title="Cell division">divide</a>. Several of these receptors are <a href="/wiki/Kinase" title="Kinase">kinases</a> that start to phosphorylate themselves and other proteins when binding to a ligand. This <a href="/wiki/Phosphorylation" title="Phosphorylation">phosphorylation</a> can generate a binding site for a different protein and thus induce protein–protein interaction. In this case, the ligand (called <a href="/wiki/Epidermal_growth_factor" title="Epidermal growth factor">epidermal growth factor</a>, or EGF) binds to the receptor (called <a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">EGFR</a>). This activates the receptor to phosphorylate itself. The phosphorylated receptor binds to an <a href="/wiki/Signal_transducing_adaptor_protein" title="Signal transducing adaptor protein">adaptor protein</a> (<a href="/wiki/GRB2" title="GRB2">GRB2</a>), which couples the signal to further downstream signaling processes. For example, one of the signal transduction pathways that are activated is called the <a href="/wiki/Mitogen-activated_protein_kinase" title="Mitogen-activated protein kinase">mitogen-activated protein kinase</a> (MAPK) pathway. The signal transduction component labeled as "MAPK" in the pathway was originally called "ERK," so the pathway is called the <a href="/wiki/MAPK/ERK_pathway" title="MAPK/ERK pathway">MAPK/ERK pathway</a>. The MAPK protein is an enzyme, a <a href="/wiki/Protein_kinase" title="Protein kinase">protein kinase</a> that can attach <a href="/wiki/Phosphate" title="Phosphate">phosphate</a> to target proteins such as the <a href="/wiki/Transcription_factor" title="Transcription factor">transcription factor</a> <a href="/wiki/C-myc" class="mw-redirect" title="C-myc">MYC</a> and, thus, alter gene transcription and, ultimately, cell cycle progression. Many cellular proteins are activated downstream of the growth factor receptors (such as EGFR) that initiate this signal transduction pathway.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (January 2011)">citation needed</span></a></i>]</sup> </p><p>Some signaling transduction pathways respond differently, depending on the amount of signaling received by the cell. For instance, the <a href="/wiki/Hedgehog_(cell_signaling)" class="mw-redirect" title="Hedgehog (cell signaling)">hedgehog protein</a> activates different genes, depending on the amount of hedgehog protein present.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (January 2011)">citation needed</span></a></i>]</sup> </p><p>Complex multi-component signal transduction pathways provide opportunities for feedback, signal amplification, and interactions inside one cell between multiple signals and signaling pathways.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (January 2011)">citation needed</span></a></i>]</sup> </p><p>A specific cellular response is the result of the transduced signal in the final stage of cell signaling. This response can essentially be any cellular activity that is present in a body. It can spur the rearrangement of the cytoskeleton, or even as catalysis by an enzyme. These three steps of cell signaling all ensure that the right cells are behaving as told, at the right time, and in synchronization with other cells and their own functions within the organism. At the end, the end of a signal pathway leads to the regulation of a cellular activity. This response can take place in the nucleus or in the cytoplasm of the cell. A majority of signaling pathways control protein synthesis by turning certain genes on and off in the nucleus. <sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> </p><p>In unicellular organisms such as bacteria, signaling can be used to 'activate' peers from a <a href="/wiki/Dormancy" title="Dormancy">dormant state</a>, enhance <a href="/wiki/Virulence" title="Virulence">virulence</a>, defend against <a href="/wiki/Bacteriophage" title="Bacteriophage">bacteriophages</a>, etc.<sup id="cite_ref-pmid9671779_46-0" class="reference"><a href="#cite_note-pmid9671779-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> In <a href="/wiki/Quorum_sensing" title="Quorum sensing">quorum sensing</a>, which is also found in social insects, the multiplicity of individual signals has the potentiality to create a positive feedback loop, generating coordinated response. In this context, the signaling molecules are called <a href="/wiki/Autoinducer" title="Autoinducer">autoinducers</a>.<sup id="cite_ref-miller_47-0" class="reference"><a href="#cite_note-miller-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid15908344_48-0" class="reference"><a href="#cite_note-pmid15908344-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid16497924_49-0" class="reference"><a href="#cite_note-pmid16497924-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> This signaling mechanism may have been involved in <a href="/wiki/Evolution" title="Evolution">evolution</a> from unicellular to multicellular organisms.<sup id="cite_ref-miller_47-1" class="reference"><a href="#cite_note-miller-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid10343281_50-0" class="reference"><a href="#cite_note-pmid10343281-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> Bacteria also use contact-dependent signaling, notably to limit their growth.<sup id="cite_ref-pmid19246237_51-0" class="reference"><a href="#cite_note-pmid19246237-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> </p><p>Signaling molecules used by multicellular organisms are often called <a href="/wiki/Pheromone" title="Pheromone">pheromones</a>. They can have such purposes as alerting against danger, indicating food supply, or assisting in reproduction.<sup id="cite_ref-52" class="reference"><a href="#cite_note-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Short-term_cellular_responses">Short-term cellular responses</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=20" title="Edit section: Short-term cellular responses"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <table class="wikitable"> <caption>Brief overview of some signaling pathways (based on receptor families) that result in short-acting cellular responses </caption> <tbody><tr> <th>Receptor Family </th> <th>Example of Ligands/ activators (Bracket: receptor for it) </th> <th>Example of <a href="/wiki/Effector_(biology)" title="Effector (biology)">effectors</a> </th> <th>Further downstream effects </th></tr> <tr> <td>Ligand Gated Ion Channels </td> <td><a href="/wiki/Acetylcholine" title="Acetylcholine">Acetylcholine</a> <br /> (such as <a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">Nicotinic acetylcholine receptor</a>), </td> <td>Changes in membrane permeability </td> <td>Change in membrane potential </td></tr> <tr> <td><a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">Seven Helix Receptor</a> </td> <td>Light (<a href="/wiki/Rhodopsin" title="Rhodopsin">Rhodopsin</a>), <br /> <a href="/wiki/Dopamine" title="Dopamine">Dopamine</a> (<a href="/wiki/Dopamine_receptor" title="Dopamine receptor">Dopamine receptor</a>), <br /> <a href="/wiki/GABA" title="GABA">GABA</a> (<a href="/wiki/GABA_receptor" title="GABA receptor">GABA receptor</a>), <br /> <a href="/wiki/Prostaglandin" title="Prostaglandin">Prostaglandin</a> (<a href="/wiki/Prostaglandin_receptor" title="Prostaglandin receptor">prostaglandin receptor</a>) etc. </td> <td>Trimeric <a href="/wiki/G_protein" title="G protein">G protein</a> </td> <td><a href="/wiki/Adenylyl_cyclase" title="Adenylyl cyclase">Adenylate Cyclase</a>, <br /> cGMP phosphodiesterase, <br /> <a href="/wiki/G_protein-gated_ion_channel" title="G protein-gated ion channel">G-protein gated ion channel</a>, etc. </td></tr> <tr> <td><a href="/wiki/Two-component_regulatory_system" title="Two-component regulatory system">Two-component</a> </td> <td>Diverse activators </td> <td>Histidine Kinase </td> <td>Response Regulator - flagellar movement, Gene expression </td></tr> <tr> <td>Membrane Guanylyl Cyclase </td> <td><a href="/wiki/Atrial_natriuretic_peptide" title="Atrial natriuretic peptide">Atrial natriuretic peptide</a>, <br /> Sea urchin egg peptide etc. </td> <td><a href="/wiki/Cyclic_guanosine_monophosphate" title="Cyclic guanosine monophosphate">cGMP</a> </td> <td>Regulation of Kinases and channels- Diverse actions </td></tr> <tr> <td>Cytoplasmic Guanylyl cyclase </td> <td><a href="/wiki/Nitric_Oxide" class="mw-redirect" title="Nitric Oxide">Nitric Oxide</a> (<a href="/wiki/Nitric_oxide_receptor" class="mw-redirect" title="Nitric oxide receptor">Nitric oxide receptor</a>) </td> <td><a href="/wiki/Cyclic_guanosine_monophosphate" title="Cyclic guanosine monophosphate">cGMP</a> </td> <td>Regulation of cGMP Gated channels, Kinases </td></tr> <tr> <td><a href="/wiki/Integrins" class="mw-redirect" title="Integrins">Integrins</a> </td> <td><a href="/wiki/Fibronectins" class="mw-redirect" title="Fibronectins">Fibronectins</a>, other extracellular matrix proteins </td> <td>Nonreceptor tyrosine kinase </td> <td>Diverse response </td></tr></tbody></table><p>.<sup id="cite_ref-Cell_biology/Pollard_et_al_53-0" class="reference"><a href="#cite_note-Cell_biology/Pollard_et_al-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-The_Cell/_G.M._Cooper_54-0" class="reference"><a href="#cite_note-The_Cell/_G.M._Cooper-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p><div class="mw-heading mw-heading3"><h3 id="Regulating_gene_activity">Regulating gene activity</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=21" title="Edit section: Regulating gene activity"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Signal_transduction_pathways.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Signal_transduction_pathways.png/500px-Signal_transduction_pathways.png" decoding="async" width="500" height="367" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Signal_transduction_pathways.png/750px-Signal_transduction_pathways.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Signal_transduction_pathways.png/1000px-Signal_transduction_pathways.png 2x" data-file-width="1858" data-file-height="1364" /></a><figcaption>Signal transduction pathways that lead to a cellular response</figcaption></figure> <table class="wikitable"> <caption>Brief overview of some signaling pathways (based on receptor families) that control gene activity </caption> <tbody><tr> <td><a href="/wiki/Frizzled" title="Frizzled">Frizzled</a> (special type of 7Helix receptor) </td> <td><a href="/wiki/Wnt_signaling_pathway" title="Wnt signaling pathway">Wnt</a> </td> <td><a href="/wiki/Dishevelled" title="Dishevelled">Dishevelled</a>, axin - APC, GSK3-beta - Beta catenin </td> <td>Gene expression </td></tr> <tr> <td><a href="/wiki/Two-component_regulatory_system" title="Two-component regulatory system">Two-component</a> </td> <td>Diverse activators </td> <td>Histidine Kinase </td> <td>Response Regulator - flagellar movement, Gene expression </td></tr> <tr> <td><a href="/wiki/Receptor_Tyrosine_Kinase" class="mw-redirect" title="Receptor Tyrosine Kinase">Receptor Tyrosine Kinase</a> </td> <td><a href="/wiki/Insulin" title="Insulin">Insulin</a> (<a href="/wiki/Insulin_receptor" title="Insulin receptor">insulin receptor</a>), <br /> <a href="/wiki/Epidermal_growth_factor" title="Epidermal growth factor">EGF</a> (<a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">EGF receptor</a>), <br /> <a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a>-Alpha, FGF-Beta, etc. (<a href="/wiki/Fibroblast_growth_factor_receptor" title="Fibroblast growth factor receptor">FGF-receptors</a>) </td> <td><a href="/wiki/Ras_protein" class="mw-redirect" title="Ras protein">Ras</a>, <a href="/wiki/Mitogen-activated_protein_kinase" title="Mitogen-activated protein kinase">MAP-kinases</a>, <a href="/wiki/Phospholipase_C" title="Phospholipase C">PLC</a>, <a href="/wiki/Phosphoinositide_3-kinase" title="Phosphoinositide 3-kinase">PI3-Kinase</a> </td> <td>Gene expression change </td></tr> <tr> <td><a href="/wiki/Cytokine_receptors" class="mw-redirect" title="Cytokine receptors">Cytokine receptors</a> </td> <td>Erythropoietin, <br /> <a href="/wiki/Growth_Hormone" class="mw-redirect" title="Growth Hormone">Growth Hormone</a> (<a href="/wiki/Growth_hormone_receptor" title="Growth hormone receptor">Growth Hormone Receptor</a>), <br /> <a href="/wiki/Interferon_gamma" title="Interferon gamma">IFN-Gamma</a> (<a href="/wiki/Interferon-gamma_receptor" title="Interferon-gamma receptor">IFN-Gamma receptor</a>) etc. </td> <td><a href="/wiki/Janus_kinase" title="Janus kinase">JAK kinase</a> </td> <td><a href="/wiki/STAT_protein" title="STAT protein">STAT transcription factor</a> - Gene expression </td></tr> <tr> <td>Tyrosine kinase Linked- receptors </td> <td>MHC-peptide complex - TCR, Antigens - BCR </td> <td>Cytoplasmic Tyrosine Kinase </td> <td>Gene expression </td></tr> <tr> <td><a href="/wiki/Receptor_protein_serine/threonine_kinase" title="Receptor protein serine/threonine kinase">Receptor Serine/Threonine Kinase</a> </td> <td><a href="/wiki/Activin" class="mw-redirect" title="Activin">Activin</a> (<a href="/wiki/Activin_receptor" title="Activin receptor">activin receptor</a>), <br /> <a href="/wiki/Inhibin" class="mw-redirect" title="Inhibin">Inhibin</a>, <br /> <a href="/wiki/Bone_morphogenetic_protein" title="Bone morphogenetic protein">Bone-morphogenetic protein</a> (<a href="/wiki/Bone_morphogenetic_protein_receptor" title="Bone morphogenetic protein receptor">BMP Receptor</a>), <br /> <a href="/wiki/Transforming_growth_factor_beta" title="Transforming growth factor beta">TGF-beta</a> </td> <td><a href="/wiki/SMAD_(protein)" title="SMAD (protein)">Smad</a> transcription factors </td> <td>Control of gene expression </td></tr> <tr> <td>Sphingomyelinase linked receptors </td> <td><a href="/wiki/Interleukin-1_family" title="Interleukin-1 family">IL-1</a> (<a href="/wiki/Interleukin-1_receptor" title="Interleukin-1 receptor">IL-1 receptor</a>), <br /> <a href="/wiki/Tumor_necrosis_factor" title="Tumor necrosis factor">TNF</a> (<a href="/wiki/TNF_receptor_superfamily" title="TNF receptor superfamily">TNF-receptors</a>) </td> <td>Ceramide activated kinases </td> <td>Gene expression </td></tr> <tr> <td>Cytoplasmic Steroid receptors </td> <td><a href="/wiki/Steroid_hormones" class="mw-redirect" title="Steroid hormones">Steroid hormones</a>, <br /> <a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">Thyroid hormones</a>, <br /> <a href="/wiki/Retinoic_acid" title="Retinoic acid">Retinoic acid</a> etc. </td> <td>Work as/ interact with transcription factors </td> <td>Gene expression </td></tr></tbody></table><p>.<sup id="cite_ref-Cell_biology/Pollard_et_al_53-1" class="reference"><a href="#cite_note-Cell_biology/Pollard_et_al-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-The_Cell/_G.M._Cooper_54-1" class="reference"><a href="#cite_note-The_Cell/_G.M._Cooper-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p><div class="mw-heading mw-heading4"><h4 id="Notch_signaling_pathway">Notch signaling pathway</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=22" title="Edit section: Notch signaling pathway"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Notchccr.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/0/04/Notchccr.svg/220px-Notchccr.svg.png" decoding="async" width="220" height="205" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/04/Notchccr.svg/330px-Notchccr.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/04/Notchccr.svg/440px-Notchccr.svg.png 2x" data-file-width="500" data-file-height="465" /></a><figcaption><i><a href="/wiki/Notch_signaling_pathway" title="Notch signaling pathway">Notch</a></i>-mediated juxtacrine signal between adjacent cells</figcaption></figure> <p><a href="/wiki/Notch_signaling_pathway" title="Notch signaling pathway">Notch</a> is a cell surface protein that functions as a receptor. Animals have a small set of <a href="/wiki/Gene" title="Gene">genes</a> that code for signaling proteins that interact specifically with Notch receptors and stimulate a response in cells that express Notch on their surface. Molecules that activate (or, in some cases, inhibit) receptors can be classified as hormones, <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a>, <a href="/wiki/Cytokine" title="Cytokine">cytokines</a>, and <a href="/wiki/Growth_factors" class="mw-redirect" title="Growth factors">growth factors</a>, in general called <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">receptor ligands</a>. Ligand receptor interactions such as that of the Notch receptor interaction, are known to be the main interactions responsible for cell signaling mechanisms and communication.<sup id="cite_ref-55" class="reference"><a href="#cite_note-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Notch_signaling_pathway" title="Notch signaling pathway">notch</a> acts as a receptor for ligands that are expressed on adjacent cells. While some receptors are cell-surface proteins, others are found inside cells. For example, <a href="/wiki/Estrogen" title="Estrogen">estrogen</a> is a <a href="/wiki/Hydrophobic" class="mw-redirect" title="Hydrophobic">hydrophobic</a> molecule that can pass through the <a href="/wiki/Lipid_bilayer" title="Lipid bilayer">lipid bilayer</a> of the <a href="/wiki/Cell_membrane" title="Cell membrane">membranes</a>. As part of the <a href="/wiki/Endocrine_system" title="Endocrine system">endocrine system</a>, intracellular <a href="/wiki/Estrogen_receptor" title="Estrogen receptor">estrogen receptors</a> from a variety of cell types can be activated by estrogen produced in the <a href="/wiki/Ovary" title="Ovary">ovaries</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (September 2023)">citation needed</span></a></i>]</sup> </p><p>In the case of Notch-mediated signaling, the signal transduction mechanism can be relatively simple. As shown in Figure 2, the activation of Notch can cause the Notch protein to be altered by a <a href="/wiki/Protease" title="Protease">protease</a>. Part of the Notch protein is released from the cell surface membrane and takes part in <a href="/wiki/Gene_regulation" class="mw-redirect" title="Gene regulation">gene regulation</a>. Cell signaling research involves studying the spatial and temporal dynamics of both receptors and the components of signaling pathways that are activated by receptors in various cell types.<sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup> Emerging methods for single-cell mass-spectrometry analysis promise to enable studying signal transduction with single-cell resolution.<sup id="cite_ref-58" class="reference"><a href="#cite_note-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup> </p><p>In <a href="/wiki/Notch_signaling" class="mw-redirect" title="Notch signaling">notch signaling</a>, direct contact between cells allows for precise control of cell <a href="/wiki/Differentiation_(cellular)" class="mw-redirect" title="Differentiation (cellular)">differentiation</a> during embryonic development. In the worm <i><a href="/wiki/Caenorhabditis_elegans" title="Caenorhabditis elegans">Caenorhabditis elegans</a></i>, two cells of the developing <a href="/wiki/Gonad" title="Gonad">gonad</a> each have an equal chance of terminally differentiating or becoming a uterine precursor cell that continues to divide. The choice of which cell continues to divide is controlled by competition of cell surface signals. One cell will happen to produce more of a cell surface protein that activates the Notch <a href="#Receptors">receptor</a> on the adjacent cell. This activates a <a href="/wiki/Feedback_loop" class="mw-redirect" title="Feedback loop">feedback loop</a> or system that reduces Notch expression in the cell that will differentiate and that increases Notch on the surface of the cell that continues as a <a href="/wiki/Stem_cell" title="Stem cell">stem cell</a>.<sup id="cite_ref-Greenwald1998_59-0" class="reference"><a href="#cite_note-Greenwald1998-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=23" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1184024115">.mw-parser-output .div-col{margin-top:0.3em;column-width:30em}.mw-parser-output .div-col-small{font-size:90%}.mw-parser-output .div-col-rules{column-rule:1px solid #aaa}.mw-parser-output .div-col dl,.mw-parser-output .div-col ol,.mw-parser-output .div-col ul{margin-top:0}.mw-parser-output .div-col li,.mw-parser-output .div-col dd{page-break-inside:avoid;break-inside:avoid-column}</style><div class="div-col"> <ul><li><a href="/wiki/Scaffold_protein" title="Scaffold protein">Scaffold protein</a></li> <li><a href="/wiki/Biosemiotics" title="Biosemiotics">Biosemiotics</a></li> <li><a href="/wiki/Molecular_cellular_cognition" title="Molecular cellular cognition">Molecular cellular cognition</a></li> <li><a href="/wiki/Crosstalk_(biology)" title="Crosstalk (biology)">Crosstalk (biology)</a></li> <li><a href="/wiki/Bacterial_outer_membrane_vesicles" class="mw-redirect" title="Bacterial outer membrane vesicles">Bacterial outer membrane vesicles</a></li> <li><a href="/wiki/Membrane_vesicle_trafficking" title="Membrane vesicle trafficking">Membrane vesicle trafficking</a></li> <li><a href="/wiki/Host%E2%80%93pathogen_interaction" title="Host–pathogen interaction">Host–pathogen interaction</a></li> <li><a href="/wiki/Retinoic_acid" title="Retinoic acid">Retinoic acid</a></li> <li><a href="/wiki/JAK-STAT_signaling_pathway" title="JAK-STAT signaling pathway">JAK-STAT signaling pathway</a></li> <li><a href="/wiki/Imd_pathway" title="Imd pathway">Imd pathway</a></li> <li><a href="/wiki/Signal_peptide" title="Signal peptide">Localisation signal</a></li> <li><a href="/wiki/Oscillation_(cell_signaling)" title="Oscillation (cell signaling)">Oscillation</a></li> <li><a href="/wiki/Protein_dynamics" title="Protein dynamics">Protein dynamics</a></li> <li><a href="/wiki/Systems_biology" title="Systems biology">Systems biology</a></li> <li><a href="/wiki/Lipid_signaling" title="Lipid signaling">Lipid signaling</a></li> <li><a href="/wiki/Redox_signaling" class="mw-redirect" title="Redox signaling">Redox signaling</a></li> <li><a href="/wiki/Signaling_cascade" class="mw-redirect" title="Signaling cascade">Signaling cascade</a></li> <li><a href="/wiki/Cell_Signaling_Technology" title="Cell Signaling Technology">Cell Signaling Technology</a> – an antibody development and production company</li> <li><a href="/wiki/Netpath" class="mw-redirect" title="Netpath">Netpath</a> – a curated resource of signal transduction pathways in humans</li> <li><a href="/wiki/Synthetic_Biology_Open_Language" title="Synthetic Biology Open Language">Synthetic Biology Open Language</a></li> <li><a href="/wiki/Nanoscale_networking" class="mw-redirect" title="Nanoscale networking">Nanoscale networking</a> – leveraging biological signaling to construct ad hoc in vivo communication networks</li> <li><a href="/wiki/Soliton_model_in_neuroscience" title="Soliton model in neuroscience">Soliton model in neuroscience</a> – physical communication via sound waves in membranes</li> <li><a href="/wiki/Temporal_feedback" title="Temporal feedback">Temporal feedback</a></li></ul> </div> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=24" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output 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.refbegin-hanging-indents>ul{margin-left:0}.mw-parser-output .refbegin-hanging-indents>ul>li{margin-left:0;padding-left:3.2em;text-indent:-3.2em}.mw-parser-output .refbegin-hanging-indents ul,.mw-parser-output .refbegin-hanging-indents ul li{list-style:none}@media(max-width:720px){.mw-parser-output .refbegin-hanging-indents>ul>li{padding-left:1.6em;text-indent:-1.6em}}.mw-parser-output .refbegin-columns{margin-top:0.3em}.mw-parser-output .refbegin-columns ul{margin-top:0}.mw-parser-output .refbegin-columns li{page-break-inside:avoid;break-inside:avoid-column}@media screen{.mw-parser-output .refbegin{font-size:90%}}</style><div class="refbegin" style=""> <ul><li>"The Inside Story of Cell Communication". <i>learn.genetics.utah.edu</i>. Retrieved 2018-10-20.</li> <li>"When Cell Communication Goes Wrong". <i>learn.genetics.utah.edu</i>. Retrieved 2018-10-24.</li></ul> </div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cell_signaling&action=edit&section=26" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" href="https://web.archive.org/web/20070715233022/http://pid.nci.nih.gov/">NCI-Nature Pathway Interaction Database</a>: authoritative information about signaling pathways in human cells.</li> <li><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=Intercellular+Signaling+Peptides+and+Proteins">Intercellular+Signaling+Peptides+and+Proteins</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li> <li><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=Cell+Communication">Cell+Communication</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li> <li><a rel="nofollow" class="external text" href="https://www.signalingpathways.org">Signaling Pathways Project</a>: cell signaling hypothesis generation knowledgebase constructed using biocurated archived transcriptomic and ChIP-Seq datasets</li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl 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.navbox-image img{max-width:none!important}@media print{body.ns-0 .mw-parser-output .navbox{display:none!important}}</style></div><div role="navigation" class="navbox" aria-labelledby="Cell_signaling_/_Signal_transduction" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Signal_transduction" title="Template:Signal transduction"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Signal_transduction" title="Template talk:Signal transduction"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Signal_transduction" title="Special:EditPage/Template:Signal transduction"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Cell_signaling_/_Signal_transduction" style="font-size:114%;margin:0 4em"><a class="mw-selflink selflink">Cell signaling</a> / <a href="/wiki/Signal_transduction" title="Signal transduction">Signal transduction</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Signaling pathways</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">GPCR</a></li> <li class="mw-empty-elt"></li> <li><a href="/wiki/Wnt_signaling_pathway" title="Wnt signaling pathway">Wnt</a></li> <li><a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">RTK</a> <ul><li><a href="/wiki/TGF_beta_signaling_pathway" title="TGF beta signaling pathway">TGF beta</a></li> <li><a href="/wiki/MAPK/ERK_pathway" title="MAPK/ERK pathway">MAPK/ERK</a></li></ul></li> <li><a href="/wiki/Notch_signaling_pathway" title="Notch signaling pathway">Notch</a></li> <li><a href="/wiki/JAK-STAT_signaling_pathway" title="JAK-STAT signaling pathway">JAK-STAT</a></li> <li><a href="/wiki/Akt/PKB_signaling_pathway" title="Akt/PKB signaling pathway">Akt/PKB</a></li> <li><a href="/wiki/Apoptosis" title="Apoptosis">Fas apoptosis</a></li> <li><a href="/wiki/Hippo_signaling_pathway" title="Hippo signaling pathway">Hippo</a></li> <li><a href="/wiki/PI3K/AKT/mTOR_pathway" title="PI3K/AKT/mTOR pathway">PI3K/AKT/mTOR pathway</a></li> <li><a href="/wiki/Integrin#Signal_transduction" title="Integrin">Integrin receptors</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Agents</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">Receptor ligands</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hormone" title="Hormone">Hormones</a></li> <li><a href="/wiki/Neurotransmitter" title="Neurotransmitter">Neurotransmitters</a>/<a href="/wiki/Neuropeptide" title="Neuropeptide">Neuropeptides</a>/<a href="/wiki/Neurohormone" title="Neurohormone">Neurohormones</a></li> <li><a href="/wiki/Cytokine" title="Cytokine">Cytokines</a></li> <li><a href="/wiki/Growth_factor" title="Growth factor">Growth factors</a></li> <li><a class="mw-selflink selflink">Signaling molecules</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptors</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">Cell surface</a></li> <li><a href="/wiki/Intracellular_receptor" title="Intracellular receptor">Intracellular</a></li> <li><a href="/wiki/Co-receptor" title="Co-receptor">Co-receptor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Second_messenger_system" title="Second messenger system">Second messenger</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CAMP-dependent_pathway" title="CAMP-dependent pathway">cAMP-dependent pathway</a></li> <li><a href="/wiki/Calcium_signaling" title="Calcium signaling">Ca<sup>2+</sup> signaling</a></li> <li><a href="/wiki/Lipid_signaling" title="Lipid signaling">Lipid signaling</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Assistants:</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Signal_transducing_adaptor_protein" title="Signal transducing adaptor protein">Signal transducing adaptor protein</a></li> <li><a href="/wiki/Scaffold_protein" title="Scaffold protein">Scaffold protein</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Transcription_factor" title="Transcription factor">Transcription factors</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/General_transcription_factor" title="General transcription factor">General</a></li> <li><a href="/wiki/Transcription_preinitiation_complex" title="Transcription preinitiation complex">Transcription preinitiation complex</a></li> <li><a href="/wiki/Transcription_factor_II_D" title="Transcription factor II D">TFIID</a></li> <li><a href="/wiki/Transcription_factor_II_H" title="Transcription factor II H">TFIIH</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">By distance</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Juxtacrine_signalling" title="Juxtacrine signalling">Juxtacrine</a></li> <li><a href="/wiki/Autocrine_signalling" class="mw-redirect" title="Autocrine signalling">Autocrine</a> / <a href="/wiki/Paracrine_signalling" class="mw-redirect" title="Paracrine signalling">Paracrine</a></li> <li><a href="/wiki/Endocrine_system" title="Endocrine system">Endocrine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other concepts</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Intracrine" title="Intracrine">Intracrine action</a></li> <li>Neurocrine signaling <ul><li><a href="/wiki/Synaptic_transmission" class="mw-redirect" title="Synaptic transmission">Synaptic transmission</a></li> <li><a href="/wiki/Chemical_synapse" title="Chemical synapse">Chemical synapse</a></li></ul></li> <li><a href="/wiki/Neuroendocrine_cell" title="Neuroendocrine cell">Neuroendocrine signaling</a></li> <li><a href="/wiki/Exocrine_gland" title="Exocrine gland">Exocrine signalling</a> <ul><li><a href="/wiki/Pheromone" title="Pheromone">Pheromones</a></li></ul></li> <li><a href="/wiki/Mechanotransduction" title="Mechanotransduction">Mechanotransduction</a></li> <li><a href="/wiki/Visual_phototransduction" title="Visual phototransduction">Phototransduction</a></li> <li><a href="/wiki/Ion_channel" title="Ion channel">Ion channel gating</a></li> <li><a href="/wiki/Gap_junction" title="Gap junction">Gap junction</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Metabolism_map" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2" style="background:#E0E0E0"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:MetabolismMap" title="Template:MetabolismMap"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:MetabolismMap" title="Template talk:MetabolismMap"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:MetabolismMap" title="Special:EditPage/Template:MetabolismMap"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Metabolism_map" style="font-size:114%;margin:0 4em"><a href="/wiki/Metabolism" title="Metabolism">Metabolism</a> map</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><div style="border:solid #ccc 1px;width:810px;margin: 0 auto"> <table role="presentation" cellpadding="0" style="border-spacing:0; margin-left: auto; margin-right: auto; border: none;"> <tbody><tr> <td><div class="thumb center" style="margin: 1em auto;"> <div class="thumbinner" style="width:802px;border:0px;background-color:#fff"> <div style="position:relative; width:800px; height:600px; overflow:hidden; border:0px; background-color:white;"> <div style="left:0px; top:0px; width:800px; position:absolute"> <span typeof="mw:File"><a href="/wiki/File:Metabolic_Metro_Map.svg" title="File:Metabolic Metro Map.svg"><img alt="Metro-style map of major metabolic pathways" src="//upload.wikimedia.org/wikipedia/commons/thumb/4/41/Metabolic_Metro_Map_%28no_legends%29.svg/800px-Metabolic_Metro_Map_%28no_legends%29.svg.png" decoding="async" width="800" height="600" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/41/Metabolic_Metro_Map_%28no_legends%29.svg/1200px-Metabolic_Metro_Map_%28no_legends%29.svg.png 1.5x, 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id="annotation_395x140" style="position:absolute; left:395px; top:140px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Pentose_phosphate_pathway" title="Pentose phosphate pathway"><span style="color:#bc00bc;">Pentose<br />phosphate<br />pathway</span></a></i> </span></div> <div id="annotation_215x340" style="position:absolute; left:215px; top:340px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Citric_acid_cycle" title="Citric acid cycle"><span style="color:#edb500;">Citric<br />acid cycle</span></a></i> </span></div> <div id="annotation_365x505" style="position:absolute; left:365px; top:505px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Glyoxylate_cycle" title="Glyoxylate cycle"><span style="color:#edb500;">Glyoxylate<br />cycle</span></a></i> </span></div> <div id="annotation_125x398" style="position:absolute; left:125px; top:398px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Urea_cycle" title="Urea cycle"><span style="color:#89dd00;">Urea<br />cycle</span></a></i> </span></div> <div id="annotation_495x260" style="position:absolute; left:495px; top:260px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Fatty_acid_synthesis" title="Fatty acid synthesis"><span style="color:#00d300;">Fatty<br />acid<br />synthesis</span></a></i> </span></div> <div id="annotation_495x335" style="position:absolute; left:495px; top:335px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Fatty_acid_synthesis" title="Fatty acid synthesis"><span style="color:#00d300;">Fatty<br />acid<br />elongation</span></a></i> </span></div> <div id="annotation_497x425" style="position:absolute; left:497px; top:425px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Beta_oxidation" title="Beta oxidation"><span style="color:#ff66cc;">Beta<br />oxidation</span></a></i> </span></div> <div id="annotation_495x495" style="position:absolute; left:495px; top:495px; font-size:12px; font-size:12; line-height:14px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Beta_oxidation#Peroxisomal_beta-oxidation" title="Beta oxidation"><span style="color:#ff66cc;">Peroxisomal</span></a></i> </span></div> <div id="annotation_497x510" style="position:absolute; left:497px; top:510px; font-size:15px; font-size:15; line-height:17px;"><span style="background-color:; color:inherit;"> <i><a href="/wiki/Beta_oxidation#Peroxisomal_beta-oxidation" title="Beta oxidation"><span style="color:#ff66cc;">beta<br />oxidation</span></a></i> </span></div> <p><br /> </p> <div id="annotation_295x42" style="position:absolute; left:295px; top:42px; font-size:9px; font-size:9; line-height:11px; text-align:right;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Glycogenolysis" title="Glycogenolysis"><span style="color:#8a2c2c;">Glyco-<br />genolysis</span></a></b></i> </span></div> <div id="annotation_280x80" style="position:absolute; left:280px; top:80px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Glycogenesis" title="Glycogenesis"><span style="color:#2e427e;">Glyco-<br />genesis</span></a></b></i> </span></div> <div id="annotation_360x160" style="position:absolute; left:360px; top:160px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Glycolysis" title="Glycolysis"><span style="color:#ea0000;">Glyco-<br />lysis</span></a></b></i> </span></div> <div id="annotation_300x160" style="position:absolute; left:300px; top:160px; font-size:9px; font-size:9; line-height:11px; text-align:right;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Gluconeogenesis" title="Gluconeogenesis"><span style="color:#0033cc;">Gluconeo-<br />genesis</span></a></b></i> </span></div> <div id="annotation_310x332" style="position:absolute; left:310px; top:332px; font-size:9px; font-size:9; line-height:11px; text-align:right;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Pyruvate_dehydrogenase" title="Pyruvate dehydrogenase"><span style="color:#ea6000;">Pyruvate<br />decarb-<br />oxylation</span></a></b></i> </span></div> <div id="annotation_365x335" style="position:absolute; left:365px; top:335px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Lactic_acid_fermentation" title="Lactic acid fermentation"><span style="color:#d47ff0;">Fermentation</span></a></b></i> </span></div> <div id="annotation_325x430" style="position:absolute; left:325px; top:430px; font-size:9px; font-size:9; line-height:11px; text-align:right;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Ketone_bodies" title="Ketone bodies"><span style="color:#e06c1f;">Keto-<br />lysis</span></a></b></i> </span></div> <div id="annotation_365x430" style="position:absolute; left:365px; top:430px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Ketogenesis" title="Ketogenesis"><span style="color:#5f8216;">Keto-<br />genesis</span></a></b></i> </span></div> <div id="annotation_195x470" style="position:absolute; left:195px; top:470px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Gluconeogenesis" title="Gluconeogenesis"><span style="color:#0033cc;">feeders to<br />gluconeo-<br />genesis</span></a></b></i> </span></div> <div id="annotation_225x230" style="position:absolute; left:225px; top:230px; font-size:9px; font-size:9; line-height:11px; text-align:right;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Carbon_fixation#Carbon_concentrating_mechanisms" class="mw-redirect" title="Carbon fixation"><span style="color:#9373d3;">Direct / C4 / CAM<br />carbon intake</span></a></b></i> </span></div> <div id="annotation_125x143" style="position:absolute; left:125px; top:143px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Light-dependent_reactions" title="Light-dependent reactions"><span style="color:#9373d3;">Light reaction</span></a></b></i> </span></div> <div id="annotation_115x355" style="position:absolute; left:115px; top:355px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Oxidative_phosphorylation" title="Oxidative phosphorylation"><span style="color:#c34747;">Oxidative<br />phosphorylation</span></a></b></i> </span></div> <div id="annotation_25x415" style="position:absolute; left:25px; top:415px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Deamination" title="Deamination"><span style="color:#4999c2;">Amino acid<br />deamination</span></a></b></i> </span></div> <div id="annotation_315x288" style="position:absolute; left:315px; top:288px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Fatty_acid_synthesis#Glycolytic_end_products_are_used_in_the_conversion_of_carbohydrates_into_fatty_acids" title="Fatty acid synthesis"><span style="color:#00d300;">Citrate<br />shuttle</span></a></b></i> </span></div> <div id="annotation_590x415" style="position:absolute; left:590px; top:415px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Lipogenesis" title="Lipogenesis"><span style="color:#00d300;">Lipogenesis</span></a></b></i> </span></div> <div id="annotation_590x455" style="position:absolute; left:590px; top:455px; font-size:9px; font-size:9; line-height:11px; text-align:left;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Lipolysis" title="Lipolysis"><span style="color:#ff66cc;">Lipolysis</span></a></b></i> </span></div> <div id="annotation_585x260" style="position:absolute; left:585px; top:260px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Steroid#Steroidogenesis" title="Steroid"><span style="color:#0099cc;">Steroidogenesis</span></a></b></i> </span></div> <div id="annotation_470x235" style="position:absolute; left:470px; top:235px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Mevalonate_pathway" title="Mevalonate pathway"><span style="color:#0099cc;">MVA pathway</span></a></b></i> </span></div> <div id="annotation_460x210" style="position:absolute; left:460px; top:210px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Non-mevalonate_pathway" title="Non-mevalonate pathway"><span style="color:#af753a;">MEP pathway</span></a></b></i> </span></div> <div id="annotation_487x153" style="position:absolute; left:487px; top:153px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Shikimate_pathway" title="Shikimate pathway"><span style="color:#00cc99;">Shikimate<br />pathway</span></a></b></i> </span></div> <div id="annotation_555x105" style="position:absolute; left:555px; top:105px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Transcription_(genetics)" class="mw-redirect" title="Transcription (genetics)"><span style="color:#79793d;">Transcription &</span></a><br /><a href="/wiki/DNA_replication" title="DNA replication"><span style="color:#79793d;">replication</span></a></b></i> </span></div> <div id="annotation_600x83" style="position:absolute; left:600px; top:83px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Translation_(biology)" title="Translation (biology)"><span style="color:#79793d;">Translation</span></a></b></i> </span></div> <div id="annotation_600x57" style="position:absolute; left:600px; top:57px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Proteolysis" title="Proteolysis"><span style="color:#6666cc;">Proteolysis</span></a></b></i> </span></div> <div id="annotation_687x55" style="position:absolute; left:687px; top:55px; font-size:9px; font-size:9; line-height:11px;"><span style="background-color:; color:inherit;"> <i><b><a href="/wiki/Glycosylation" title="Glycosylation"><span style="color:#79793d;">Glycosyl-<br />ation</span></a></b></i> </span></div> <p><br /> </p> <div id="annotation_210x38" style="position:absolute; left:210px; top:38px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Sugar_acid" title="Sugar acid">Sugar<br />acids</a> </span></div> <div id="annotation_240x38" style="position:absolute; left:240px; top:38px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Disaccharide" title="Disaccharide">Double</a>/<a href="/wiki/Polysaccharide" title="Polysaccharide">multiple<br />sugars</a> & <a href="/wiki/Glycan" title="Glycan">glycans</a> </span></div> <div id="annotation_340x38" style="position:absolute; left:340px; top:38px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Monosaccharide" title="Monosaccharide">Simple<br />sugars</a> </span></div> <div id="annotation_380x45" style="position:absolute; left:380px; top:45px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Inositol_phosphate" title="Inositol phosphate">Inositol-P</a> </span></div> <div id="annotation_160x90" style="position:absolute; left:160px; top:90px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Amino_sugar" title="Amino sugar">Amino sugars</a><br />& <a href="/wiki/Sialic_acid" title="Sialic acid">sialic acids</a> </span></div> <div id="annotation_245x120" style="position:absolute; left:245px; top:120px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Nucleotide_sugar" title="Nucleotide sugar">Nucleotide sugars</a> </span></div> <div id="annotation_365x105" style="position:absolute; left:365px; top:105px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glucose_6-phosphate" title="Glucose 6-phosphate">Hexose-P</a> </span></div> <div id="annotation_315x180" style="position:absolute; left:315px; top:180px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glyceraldehyde_3-phosphate" title="Glyceraldehyde 3-phosphate">Triose-P</a> </span></div> <div id="annotation_305x240" style="position:absolute; left:305px; top:240px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glycerol" title="Glycerol">Glycerol</a> </span></div> <div id="annotation_300x260" style="position:absolute; left:300px; top:260px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Phosphoglycerate" title="Phosphoglycerate">P-glycerates</a> </span></div> <div id="annotation_425x110" style="position:absolute; left:425px; top:110px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Ribose_5-phosphate" title="Ribose 5-phosphate">Pentose-P</a> </span></div> <div id="annotation_470x190" style="position:absolute; left:470px; top:190px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Erythrose_4-phosphate" title="Erythrose 4-phosphate">Tetrose-P</a> </span></div> <div id="annotation_410x440" style="position:absolute; left:410px; top:440px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Propionyl-CoA" title="Propionyl-CoA">Propionyl<br />-CoA</a> </span></div> <div id="annotation_310x495" style="position:absolute; left:310px; top:495px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Succinic_acid" title="Succinic acid">Succinate</a> </span></div> <div id="annotation_455x530" style="position:absolute; left:455px; top:530px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Acetyl-CoA" title="Acetyl-CoA">Acetyl<br />-CoA</a> </span></div> <div id="annotation_150x155" style="position:absolute; left:150px; top:155px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Ribose_5-phosphate" title="Ribose 5-phosphate">Pentose-P</a> </span></div> <div id="annotation_230x210" style="position:absolute; left:230px; top:210px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Phosphoglycerate" title="Phosphoglycerate">P-glycerates</a> </span></div> <div id="annotation_85x180" style="position:absolute; left:85px; top:180px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glyoxylic_acid" title="Glyoxylic acid">Glyoxylate</a> </span></div> <div id="annotation_65x152" style="position:absolute; left:65px; top:152px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Photosystem" title="Photosystem">Photosystems</a> </span></div> <div id="annotation_320x310" style="position:absolute; left:320px; top:310px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Pyruvic_acid" title="Pyruvic acid">Pyruvate</a> </span></div> <div id="annotation_410x308" style="position:absolute; left:410px; top:308px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Lactic_acid" title="Lactic acid">Lactate</a> </span></div> <div id="annotation_365x345" style="position:absolute; left:365px; top:345px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Acetyl-CoA" title="Acetyl-CoA">Acetyl<br />-CoA</a> </span></div> <div id="annotation_295x380" style="position:absolute; left:295px; top:380px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Citric_acid" title="Citric acid">Citrate</a> </span></div> <div id="annotation_270x300" style="position:absolute; left:270px; top:300px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Oxaloacetic_acid" title="Oxaloacetic acid">Oxalo-<br />acetate</a> </span></div> <div id="annotation_200x310" style="position:absolute; left:200px; top:310px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Malic_acid" title="Malic acid">Malate</a> </span></div> <div id="annotation_195x405" style="position:absolute; left:195px; top:405px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Succinyl-CoA" title="Succinyl-CoA">Succinyl<br />-CoA</a> </span></div> <div id="annotation_275x405" style="position:absolute; left:275px; top:405px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Alpha-Ketoglutaric_acid" class="mw-redirect" title="Alpha-Ketoglutaric acid">α-Keto-<br />glutarate</a> </span></div> <div id="annotation_370x455" style="position:absolute; left:370px; top:455px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Ketone_bodies" title="Ketone bodies">Ketone<br />bodies</a> </span></div> <div id="annotation_70x365" style="position:absolute; left:70px; top:365px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Electron_transport_chain" title="Electron transport chain">Respiratory<br />chain</a> </span></div> <div id="annotation_370x265" style="position:absolute; left:370px; top:265px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Serine" title="Serine">Serine group</a> </span></div> <div id="annotation_395x290" style="position:absolute; left:395px; top:290px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Alanine" title="Alanine">Alanine</a> </span></div> <div id="annotation_415x345" style="position:absolute; left:415px; top:345px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Branched-chain_amino_acid" title="Branched-chain amino acid">Branched-chain<br />amino acids</a> </span></div> <div id="annotation_275x275" style="position:absolute; left:275px; top:275px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Aspartic_acid" title="Aspartic acid">Aspartate<br />group</a> </span></div> <div id="annotation_180x250" style="position:absolute; left:180px; top:250px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Homoserine" title="Homoserine">Homoserine<br />group</a><br />& <a href="/wiki/Lysine" title="Lysine">lysine</a> </span></div> <div id="annotation_280x445" style="position:absolute; left:280px; top:445px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glutamic_acid" title="Glutamic acid">Glutamate<br />group</a><br />& <a href="/wiki/Proline" title="Proline">proline</a> </span></div> <div id="annotation_105x465" style="position:absolute; left:105px; top:465px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Arginine" title="Arginine">Arginine</a> </span></div> <div id="annotation_40x465" style="position:absolute; left:40px; top:465px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Creatine" title="Creatine">Creatine</a><br />& <a href="/wiki/Polyamine" title="Polyamine">polyamines</a> </span></div> <div id="annotation_415x385" style="position:absolute; left:415px; top:385px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Ketogenic_amino_acid" title="Ketogenic amino acid">Ketogenic</a> &<br /><a href="/wiki/Glucogenic_amino_acid" title="Glucogenic amino acid">glucogenic<br />amino acids</a> </span></div> <div id="annotation_550x85" style="position:absolute; left:550px; top:85px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Amino_acid" title="Amino acid">Amino acids</a> </span></div> <div id="annotation_520x190" style="position:absolute; left:520px; top:190px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Shikimic_acid" title="Shikimic acid">Shikimate</a> </span></div> <div id="annotation_635x165" style="position:absolute; left:635px; top:165px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Aromatic_amino_acid" title="Aromatic amino acid">Aromatic amino<br />acids</a> & <a href="/wiki/Histidine" title="Histidine">histidine</a> </span></div> <div id="annotation_158x38" style="position:absolute; left:158px; top:38px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Ascorbate" class="mw-redirect" title="Ascorbate">Ascorbate</a><br />(<a href="/wiki/Vitamin_C" title="Vitamin C">vitamin C</a>) </span></div> <div id="annotation_275x490" style="position:absolute; left:275px; top:490px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Aminolevulinic_acid" title="Aminolevulinic acid">δ-ALA</a> </span></div> <div id="annotation_155x510" style="position:absolute; left:155px; top:510px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Bile_pigment" class="mw-redirect" title="Bile pigment">Bile<br />pigments</a> </span></div> <div id="annotation_210x520" style="position:absolute; left:210px; top:520px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Heme" title="Heme">Hemes</a> </span></div> <div id="annotation_245x585" style="position:absolute; left:245px; top:585px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Cobalamin" class="mw-redirect" title="Cobalamin">Cobalamins</a> (<a href="/wiki/Vitamin_B" class="mw-redirect" title="Vitamin B">vitamin B<sub>12</sub></a>) </span></div> <div id="annotation_425x45" style="position:absolute; left:425px; top:45px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Vitamin_B" class="mw-redirect" title="Vitamin B">Various<br />vitamin Bs</a> </span></div> <div id="annotation_625x300" style="position:absolute; left:625px; top:300px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Calciferol" class="mw-redirect" title="Calciferol">Calciferols</a><br />(<a href="/wiki/Vitamin_D" title="Vitamin D">vitamin D</a>) </span></div> <div id="annotation_725x235" style="position:absolute; left:725px; top:235px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Retinoid" title="Retinoid">Retinoids</a><br />(<a href="/wiki/Vitamin_A" title="Vitamin A">vitamin A</a>) </span></div> <div id="annotation_590x190" style="position:absolute; left:590px; top:190px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Quinone" title="Quinone">Quinones</a> (<a href="/wiki/Vitamin_K" title="Vitamin K">vitamin K</a>)<br />& <a href="/wiki/Tocopherol" title="Tocopherol">tocopherols</a> (<a href="/wiki/Vitamin_E" title="Vitamin E">vitamin E</a>) </span></div> <div id="annotation_665x140" style="position:absolute; left:665px; top:140px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">Cofactors</a> </span></div> <div id="annotation_745x140" style="position:absolute; left:745px; top:140px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Vitamin" title="Vitamin">Vitamins</a><br />& <a href="/wiki/Metalloprotein" title="Metalloprotein">minerals</a> </span></div> <div id="annotation_720x185" style="position:absolute; left:720px; top:185px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Antioxidant" title="Antioxidant">Antioxidants</a> </span></div> <div id="annotation_490x140" style="position:absolute; left:490px; top:140px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Phosphoribosyl_pyrophosphate" title="Phosphoribosyl pyrophosphate">PRPP</a> </span></div> <div id="annotation_535x140" style="position:absolute; left:535px; top:140px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Nucleotide" title="Nucleotide">Nucleotides</a> </span></div> <div id="annotation_610x140" style="position:absolute; left:610px; top:140px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Nucleic_acid" title="Nucleic acid">Nucleic<br />acids</a> </span></div> <div id="annotation_665x87" style="position:absolute; left:665px; top:87px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Protein" title="Protein">Proteins</a> </span></div> <div id="annotation_710x87" style="position:absolute; left:710px; top:87px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glycoprotein" title="Glycoprotein">Glycoproteins</a><br />& <a href="/wiki/Proteoglycan" title="Proteoglycan">proteoglycans</a> </span></div> <div id="annotation_280x520" style="position:absolute; left:280px; top:520px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Chlorophyll" title="Chlorophyll">Chlorophylls</a> </span></div> <div id="annotation_410x235" style="position:absolute; left:410px; top:235px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Methylerythritol_phosphate" class="mw-redirect" title="Methylerythritol phosphate">MEP</a> </span></div> <div id="annotation_420x245" style="position:absolute; left:420px; top:245px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Mevalonic_acid" title="Mevalonic acid">MVA</a> </span></div> <div id="annotation_420x260" style="position:absolute; left:420px; top:260px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Acetyl-CoA" title="Acetyl-CoA">Acetyl<br />-CoA</a> </span></div> <div id="annotation_440x330" style="position:absolute; left:440px; top:330px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Polyketide" title="Polyketide">Polyketides</a> </span></div> <div id="annotation_555x230" style="position:absolute; left:555px; top:230px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Isopentenyl_pyrophosphate" title="Isopentenyl pyrophosphate">Terpenoid<br />backbones</a> </span></div> <div id="annotation_625x235" style="position:absolute; left:625px; top:235px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Terpenoid" title="Terpenoid">Terpenoids</a><br />& <a href="/wiki/Carotenoid" title="Carotenoid">carotenoids</a> (<a href="/wiki/Vitamin_A" title="Vitamin A">vitamin A</a>) </span></div> <div id="annotation_640x287" style="position:absolute; left:640px; top:287px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Cholesterol" title="Cholesterol">Cholesterol</a> </span></div> <div id="annotation_720x287" style="position:absolute; left:720px; top:287px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Bile_acid" title="Bile acid">Bile acids</a> </span></div> <div id="annotation_640x330" style="position:absolute; left:640px; top:330px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glycerophospholipid" title="Glycerophospholipid">Glycero-<br />phospholipids</a> </span></div> <div id="annotation_600x397" style="position:absolute; left:600px; top:397px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glycerolipid" class="mw-redirect" title="Glycerolipid">Glycerolipids</a> </span></div> <div id="annotation_620x430" style="position:absolute; left:620px; top:430px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Acyl-CoA" title="Acyl-CoA">Acyl-CoA</a> </span></div> <div id="annotation_630x500" style="position:absolute; left:630px; top:500px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Fatty_acid" title="Fatty acid">Fatty<br />acids</a> </span></div> <div id="annotation_720x350" style="position:absolute; left:720px; top:350px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Glycosphingolipid" title="Glycosphingolipid">Glyco-<br />sphingolipids</a> </span></div> <div id="annotation_720x397" style="position:absolute; left:720px; top:397px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Sphingolipid" title="Sphingolipid">Sphingolipids</a> </span></div> <div id="annotation_720x440" style="position:absolute; left:720px; top:440px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Wax" title="Wax">Waxes</a> </span></div> <div id="annotation_680x497" style="position:absolute; left:680px; top:497px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Polyunsaturated_fatty_acid" class="mw-redirect" title="Polyunsaturated fatty acid">Polyunsaturated<br />fatty acids</a> </span></div> <div id="annotation_470x45" style="position:absolute; left:470px; top:45px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Neurotransmitters" class="mw-redirect" title="Neurotransmitters">Neurotransmitters</a><br />& <a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">thyroid hormones</a> </span></div> <div id="annotation_705x305" style="position:absolute; left:705px; top:305px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Steroid" title="Steroid">Steroids</a> </span></div> <div id="annotation_587x330" style="position:absolute; left:587px; top:330px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Endocannabinoid_system" title="Endocannabinoid system">Endo-<br />cannabinoids</a> </span></div> <div id="annotation_735x465" style="position:absolute; left:735px; top:465px; line-height:110%;"><span style="background-color:transparent; color:inherit;"> <a href="/wiki/Eicosanoid" title="Eicosanoid">Eicosanoids</a> </span></div></div> </div> </div> </div> </div> </td></tr></tbody></table></div><div class="thumbcaption"><div style="float:left;margin-right:0.5em"><span typeof="mw:File"><span title="The image above contains clickable links"><img alt="The image above contains clickable links" src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Interactive_icon.svg/18px-Interactive_icon.svg.png" decoding="async" width="18" height="27" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Interactive_icon.svg/27px-Interactive_icon.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Interactive_icon.svg/36px-Interactive_icon.svg.png 2x" data-file-width="133" data-file-height="200" /></span></span></div> Major <a href="/wiki/Metabolic_pathway" title="Metabolic pathway">metabolic pathways</a> in <a href="/wiki/Transit_map" title="Transit map">metro-style map</a>. Click any text (name of pathway or metabolites) to link to the corresponding article.<br />Single lines: pathways common to most lifeforms. Double lines: pathways not in humans (occurs in e.g. plants, fungi, prokaryotes). <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Metabolic_metro_orange.svg/15px-Metabolic_metro_orange.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Metabolic_metro_orange.svg/23px-Metabolic_metro_orange.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Metabolic_metro_orange.svg/30px-Metabolic_metro_orange.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Orange nodes: <a href="/wiki/Carbohydrate_metabolism" title="Carbohydrate metabolism">carbohydrate metabolism</a>.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Metabolic_metro_purple.svg/15px-Metabolic_metro_purple.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Metabolic_metro_purple.svg/23px-Metabolic_metro_purple.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Metabolic_metro_purple.svg/30px-Metabolic_metro_purple.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Violet nodes: <a href="/wiki/Photosynthesis" title="Photosynthesis">photosynthesis</a>.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Metabolic_metro_red.svg/15px-Metabolic_metro_red.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Metabolic_metro_red.svg/23px-Metabolic_metro_red.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Metabolic_metro_red.svg/30px-Metabolic_metro_red.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Red nodes: <a href="/wiki/Cellular_respiration" title="Cellular respiration">cellular respiration</a>.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/db/Metabolic_metro_pink.svg/15px-Metabolic_metro_pink.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/db/Metabolic_metro_pink.svg/23px-Metabolic_metro_pink.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/db/Metabolic_metro_pink.svg/30px-Metabolic_metro_pink.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Pink nodes: <a class="mw-selflink selflink">cell signaling</a>.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/1b/Metabolic_metro_blue.svg/15px-Metabolic_metro_blue.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/1b/Metabolic_metro_blue.svg/23px-Metabolic_metro_blue.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/1b/Metabolic_metro_blue.svg/30px-Metabolic_metro_blue.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Blue nodes: <a href="/wiki/Amino_acid_metabolism" class="mw-redirect" title="Amino acid metabolism">amino acid metabolism</a>.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c8/Metabolic_metro_grey.svg/15px-Metabolic_metro_grey.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/c8/Metabolic_metro_grey.svg/23px-Metabolic_metro_grey.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/c8/Metabolic_metro_grey.svg/30px-Metabolic_metro_grey.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Grey nodes: <a href="/wiki/Vitamin" title="Vitamin">vitamin</a> and <a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">cofactor</a> metabolism.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Metabolic_metro_brown.svg/15px-Metabolic_metro_brown.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Metabolic_metro_brown.svg/23px-Metabolic_metro_brown.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/99/Metabolic_metro_brown.svg/30px-Metabolic_metro_brown.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Brown nodes: <a href="/wiki/Nucleic_acid_metabolism" title="Nucleic acid metabolism">nucleotide</a> and <a href="/wiki/Protein_metabolism" title="Protein metabolism">protein</a> metabolism.</span> <span class="nowrap"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/97/Metabolic_metro_green.svg/15px-Metabolic_metro_green.svg.png" decoding="async" width="15" height="17" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/97/Metabolic_metro_green.svg/23px-Metabolic_metro_green.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/97/Metabolic_metro_green.svg/30px-Metabolic_metro_green.svg.png 2x" data-file-width="30" data-file-height="34" /></span></span> Green nodes: <a href="/wiki/Lipid_metabolism" title="Lipid metabolism">lipid metabolism</a>.</span></div></div></td></tr></tbody></table></div> <style data-mw-deduplicate="TemplateStyles:r1130092004">.mw-parser-output .portal-bar{font-size:88%;font-weight:bold;display:flex;justify-content:center;align-items:baseline}.mw-parser-output .portal-bar-bordered{padding:0 2em;background-color:#fdfdfd;border:1px solid #a2a9b1;clear:both;margin:1em auto 0}.mw-parser-output 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