CINXE.COM

Sonic hedgehog induces the segregation of patched and smoothened in endosomes - PubMed

<!DOCTYPE html> <html lang="en" > <head itemscope itemtype="http://schema.org/WebPage" prefix="og: http://ogp.me/ns#" > <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <!-- Mobile properties --> <meta name="HandheldFriendly" content="True"> <meta name="MobileOptimized" content="320"> <meta name="viewport" content="width=device-width, initial-scale=1.0"> <link rel="preconnect" href="https://cdn.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.google-analytics.com"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/css/output.5ecf62baa0fa.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/css/output.452c70ce66f7.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/css/output.7bf600913d6e.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/css/output.0bfa59184c7a.css" type="text/css"> <title>Sonic hedgehog induces the segregation of patched and smoothened in endosomes - PubMed</title> <link rel="preload" as="font" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/uswds/dist/fonts/merriweather-bold-webfont.woff2" type="font/woff2" crossorigin /> <!-- Favicons --> <link rel="shortcut icon" type="image/ico" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.ico" /> <link rel="icon" type="image/png" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.png" /> <!-- 192x192, as recommended for Android http://updates.html5rocks.com/2014/11/Support-for-theme-color-in-Chrome-39-for-Android --> <link rel="icon" type="image/png" sizes="192x192" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-192.png" /> <!-- 57x57 (precomposed) for iPhone 3GS, pre-2011 iPod Touch and older Android devices --> <link rel="apple-touch-icon-precomposed" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-57.png"> <!-- 72x72 (precomposed) for 1st generation iPad, iPad 2 and iPad mini --> <link rel="apple-touch-icon-precomposed" sizes="72x72" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-72.png"> <!-- 114x114 (precomposed) for iPhone 4, 4S, 5 and post-2011 iPod Touch --> <link rel="apple-touch-icon-precomposed" sizes="114x114" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-114.png"> <!-- 144x144 (precomposed) for iPad 3rd and 4th generation --> <link rel="apple-touch-icon-precomposed" sizes="144x144" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-144.png"> <!-- For Pinger + Google Optimize integration (NS-820) --> <meta name="ncbi_sg_optimize_id" content=""> <!-- Mobile browser address bar color --> <meta name="theme-color" content="#20558a"> <!-- Preserve the Referrer when going from HTTPS to HTTP --> <meta name="referrer" content="origin-when-cross-origin"> <meta name="ncbi_pinger_gtm_track" content="true"/> <!-- Logging params: Pinger defaults --> <meta name="ncbi_app" content="pubmed" /> <meta name="ncbi_db" content="pubmed" /> <meta name="ncbi_phid" content="DC760001A77F30F500002A816D2ADEDB.1.m_6" /> <meta name="ncbi_pinger_stat_url" content="https://www.ncbi.nlm.nih.gov/stat" /> <meta name="log_category" content="literature" /> <meta name="ncbi_cost_center" content="pubmed" /> <!-- Logging params: Pinger custom --> <meta name="ncbi_pdid" content="abstract" /> <meta name="log_op" content="retrieve" /> <meta name="uid" content="12123571" /> <meta name="ncbi_uid" content="12123571" /> <meta name="log_displayeduids" content="12123571" /> <meta name="log_source_db" content="pubmed" /> <meta name="log_icons_present" content="true" /> <!-- Social meta tags for unfurling urls --> <meta name="description" content="These data support a model in which Ptc1 inhibits Smo only when in the same compartment. Ligand-induced segregation allows Smo to signal independently of Ptc1 after becoming sorted from Ptc1/Shh complexes in the late endocytic pathway."><meta name="keywords" content="pmid:12123571, doi:10.1016/s0960-9822(02)00895-3, Research Support, U.S. Gov&#x27;t, P.H.S., John P Incardona, Jean Gruenberg, Henk Roelink, Animals, Biological Transport, Cell Line, Drosophila, Drosophila Proteins*, Endosomes / physiology*, Hedgehog Proteins, Membrane Proteins / physiology*, Patched Receptors, Receptors, Cell Surface / physiology*, Receptors, G-Protein-Coupled*, Signal Transduction, Smoothened Receptor, Trans-Activators / physiology*, Vertebrates, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Sonic hedgehog induces the segregation of patched and smoothened in endosomes - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/12123571/"><meta property="og:description" content="These data support a model in which Ptc1 inhibits Smo only when in the same compartment. Ligand-induced segregation allows Smo to signal independently of Ptc1 after becoming sorted from Ptc1/Shh complexes in the late endocytic pathway."><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Sonic hedgehog induces the segregation of patched and smoothened in endosomes - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/12123571/"><meta name="twitter:description" content="These data support a model in which Ptc1 inhibits Smo only when in the same compartment. Ligand-induced segregation allows Smo to signal independently of Ptc1 after becoming sorted from Ptc1/Shh complexes in the late endocytic pathway."><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"> <!-- OpenSearch XML --> <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search"> <!-- Disables severely broken elements when no JS --> <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/core/no-script.css"> </noscript> <meta name="citation_title" content="Sonic hedgehog induces the segregation of patched and smoothened in endosomes"> <meta name="citation_authors" content="Incardona JP;Gruenberg J;Roelink H;"> <meta name="citation_date" content="06/25/2002"> <meta name="citation_publisher" content="Curr Biol"> <meta name="citation_journal_title" content="Current biology : CB"> <meta name="citation_pmid" content="12123571"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/12123571/"> <meta name="citation_volume" content="12"> <meta name="citation_issue" content="12"> <meta name="citation_doi" content="10.1016/s0960-9822(02)00895-3"> <meta name="citation_issn" content="0960-9822"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/12123571/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! </div> </div> </div> </noscript> <div class="no-session-banner" id="no-session-banner" hidden> <div class="warning-message"> <div class="warning-message-text"> Clipboard, Search History, and several other advanced features are temporarily unavailable. </div> <button class="close-banner-button" title="Close Clipboard and Search History not available warning banner" ref="linksrc=close_no_session_banner" aria-controls="no-session-banner" aria-label="Close Clipboard and Search History not available warning banner" aria-expanded="true"> </button> </div> </div> <a class="usa-skipnav" href="#article-details"> Skip to main page content </a> <!-- ========== BEGIN HEADER ========== --> <section class="usa-banner"> <div class="usa-accordion"> <header class="usa-banner-header"> <div class="usa-grid usa-banner-inner"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" /> <p>An official website of the United States government</p> <button class="usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" > <span class="usa-banner-button-text">Here's how you know</span> </button> </div> </header> <div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" > <div class="usa-banner-guidance-gov usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" /> <div class="usa-media_block-body"> <p> <strong>The .gov means it鈥檚 official.</strong> <br /> Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you鈥檙e on a federal government site. </p> </div> </div> <div class="usa-banner-guidance-ssl usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" /> <div class="usa-media_block-body"> <p> <strong>The site is secure.</strong> <br /> The <strong>https://</strong> ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. </p> </div> </div> </div> </div> </section> <div class="usa-overlay"></div> <header class="ncbi-header" role="banner" data-section="Header"> <div class="usa-grid"> <div class="usa-width-one-whole"> <div class="ncbi-header__logo"> <a href="https://www.ncbi.nlm.nih.gov/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" /> </a> </div> <div class="ncbi-header__account"> <a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a> <button id="account_info" class="header-button" style="display:none" aria-controls="account_popup"> <span class="fa fa-user" aria-hidden="true"></span> <span class="username desktop-only" aria-hidden="true" id="uname_short"></span> <span class="sr-only">Show account info</span> </button> </div> <div class="ncbi-popup-anchor"> <div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true"> <div class="ncbi-popup-head"> <button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu"><span class="fa fa-times"></span><span class="usa-sr-only">Close</span></button> <h4>Account</h4> </div> <div class="account-user-info"> Logged in as:<br/> <b><span class="username" id="uname_long">username</span></b> </div> <div class="account-links"> <ul class="usa-unstyled-list"> <li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li> <li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li> <li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li> <li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li> </ul> </div> </div> </div> </div> </div> </header> <div role="navigation" aria-label="access keys"> <a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a> <a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a> <a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a> <a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a> <a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a> </div> <section data-section="Alerts"> <div class="ncbi-alerts-placeholder"></div> </section> <!-- ========== END HEADER ========== --> <a id="maincontent" aria-label="Main page content below" role="navigation"></a> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <form action="/" method="get" autocomplete="off" class="usa-search usa-search-big search-form content-page-layout" id="search-form" role="search"> <div class="inner-wrap"> <a class="pubmed-logo" aria-label="Pubmed Logo" href="/" data-ga-category="featured_link" data-ga-action="pubmed_logo"> <img src="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/core/images/pubmed-logo-blue.svg" alt="pubmed logo" /> </a> <a href="#" class="search-input-trigger" data-alt-title="Hide search bar" title="Show search bar" aria-label="Show search bar"> </a> <div role="search" class="search-input"> <div class="form-field "> <label class="usa-sr-only" for="id_term"> Search: </label> <input type="search" name="term" data-skip-ie-scroll-to-top="" data-replace-term-with-exact="" data-exact-query="" placeholder="" class="term-input" required="required" id="id_term"/><a href="#" class="clear-btn" aria-label="Clear search input" title="Clear search input" role="button" data-pinger-ignore></a><button type="submit" class="search-btn" aria-label="Search" disabled data-pinger-ignore><span class="usa-search-submit-text">Search</span></button> </div> </div> <!-- Create alert and Create RSS are buttons that look like links --> <!-- Better for them to look like buttons but no space --> <div class="search-links-wrapper content-page-layout"> <div class="search-links"> <a href="/advanced/" class="search-input-link adv-search-link" data-ga-category="featured_link" data-ga-action="adv_search">Advanced</a> <a href="/clipboard/" class="search-input-link clipboard-link hidden" data-ga-category="featured_link" data-ga-action="clipboard"> Clipboard <span class="amount-in-clipboard"></span> </a> </div> <span class="search-input-link user-guide-link" role="navigation" aria-label="User guide"> <a href="/help/" data-ga-category="featured_link" data-ga-action="user_guide"> User Guide </a> </span> </div> </div> </form> <div id="article-page-header"> <div id="article-top-actions-bar" class="article-top-actions-bar"> <div class="inner-wrap"> <div class="actions-container"> <div class="return-to-search"> </div> <div class="multiple-results-actions " role="region" aria-label="save, email, send to"> <button id="save-results-panel-trigger" type="button" class="save-results save-results-panel-trigger" aria-expanded="false" aria-controls="save-action-panel" data-ga-category="save_share" data-ga-action="save" data-ga-label="open"> Save </button><button id="email-results-panel-trigger" type="button" class="email-results email-results-panel-trigger" aria-expanded="false" aria-controls="email-action-panel" data-ga-category="save_share" data-ga-action="email" data-ga-label="open"> Email </button><div class="more-actions dropdown-block"><button id="more-actions-trigger" type="button" class="trigger more-actions-trigger" ref="linksrc=show_moreactions_btn" aria-label="Send to" aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link " href="#" role="button" data-ga-category="save_share" data-ga-action="clipboard" data-ga-label="send"> Clipboard </a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div> </div> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> </div> </div> </div> <div id="article-panels-container" class="article-panels-container"> <div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Save citation to file </h2> <form id="save-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="action-panel-control-wrap"> <label for="save-action-format" class="action-panel-label"> Format: </label> <select id="save-action-format" name="results-format" class="action-panel-selector"> <option value="summary-text">Summary (text)</option> <option value="pubmed-text">PubMed</option> <option value="pmid">PMID</option> <option value="abstract">Abstract (text)</option> <option value="csv">CSV</option> </select> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="save" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Save citations to file' panel" ref="linksrc=close_save_panel" aria-controls="save-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="save" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="email-action-panel" class="email-action-panel action-panel" aria-hidden="true" data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback" data-recaptcha-enabled="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Email citation </h2> <form id="email-action-panel-form" class="action-panel-content action-form" action="/send-email/" data-by-search-action="/results-export-email-by-search-data/" data-by-ids-action="/send-email/" data-by-search-method="post" data-by-ids-method="post" method="post" > <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="action-panel-control-wrap"> <span class="action-panel-label"> Subject: </span> <span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 12123571 - PubMed</span> <input type="hidden" name="email-subject" value="1 selected item: 12123571"/> <input type="hidden" name="email-subject-hash" value="7ecfda0f59443763ea20e3a81803a3256479c964a5a2c5a60c7dd0663c4cb951"/> </div> <div class="action-panel-control-wrap"> <label for="email-to" class="action-panel-label required-field-asterisk"> To: </label> <input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required> </div> <div class="action-panel-control-wrap"> <label for="email-from" class="action-panel-label"> From: </label> <input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256"> </div> <div class="action-panel-control-wrap"> <label for="email-citation-format" class="action-panel-label"> Format: </label> <select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format"> <option selected="selected" value="summary">Summary</option> <option value="summary-text">Summary (text)</option> <option value="abstract">Abstract</option> <option value="abstract-text">Abstract (text)</option> </select> </div> <div class="include-supplemental-container"> <input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental"> <label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label> </div> <div class="form-field recaptcha "> <div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div> </div> <div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="email" data-ga-label="send"> Send email </button> <button class="action-panel-cancel" aria-label="Close 'Email citations' panel" ref="linksrc=close_email_panel" aria-controls="email-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="email" data-ga-label="cancel"> Cancel </button> </div> <input type="hidden" name="email-search-details" value="" /> <input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" /> </form> </div> </div> <div id="collections-action-panel" class="collections-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-collections-open-panel-enabled="false" data-collections-open-panel-url-hash="#open-collections-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to Collections </h3> <form id="collections-action-panel-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="choice-group" role="radiogroup"> <ul class="radio-group-items"> <li> <input type="radio" id="collections-action-panel-new" class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="12123571"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(02)00895-3" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=12123571&amp;db=pubmed&amp;nlmid=9107782" title="See full text options at Elsevier Science" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="12123571" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="full text provider logo"><span class="text"> Elsevier Science </span></a> </div> </div> <div class="short-view"> <a href="#" class="full-text-links-button full-text-links-dialog-trigger"> Full text links </a> </div> </div> <div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/12123571/citations/" data-citation-style="nlm" data-pubmed-format-link="/12123571/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="12123571" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger" aria-label="Save article in MyNCBI collections." data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_button" data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="sidebar-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="social-sharing"> <h3 class="title"> Share </h3> <ul class="social-sharing-links usa-unstyled-list"> <li> <a href="http://twitter.com/intent/tweet?text=Sonic%20hedgehog%20induces%20the%20segregation%20of%20patched%20and%20smoothened%20in%20endosomes%20https%3A//pubmed.ncbi.nlm.nih.gov/12123571/" class="share-link share-link-twitter" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Twitter" data-ga-category="save_share" data-ga-action="social" data-ga-label="twitter"></a> </li> <li> <a href="http://www.facebook.com/sharer/sharer.php?u=https%3A//pubmed.ncbi.nlm.nih.gov/12123571/" class="share-link share-link-facebook" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Facebook" data-ga-category="save_share" data-ga-action="social" data-ga-label="fb"></a> </li> <li> <div class="share-permalink"> <button class="trigger" title="Show article permalink" ref="linksrc=show_permalink_btn"> </button> <div class="dropdown" hidden> <div class="title"> Permalink </div> <div class="content"> <input type="text" class="permalink-text" value="https://pubmed.ncbi.nlm.nih.gov/12123571/" aria-label="Article permalink"/><button class="permalink-copy-button usa-button-primary" title="Copy article permalink" data-ga-category="save_share" data-ga-action="link" data-ga-label="copy_link"><span class="button-title">Copy</span></button> </div> </div> </div> </li> </ul> </div> <nav class="page-navigator" role="navigation" aria-label="Page navigation"> <div class="full-view"> <h3 class="title"> Page navigation </h3> <ul class="items-list"> <li class="heading "> <a href="#heading" aria-label="navigate to Title &amp; authors section" data-ga-category="page_nav" data-ga-action="heading"> Title &amp; authors </a> </li> <li class="abstract "> <a href="#abstract" aria-label="navigate to Abstract section" data-ga-category="page_nav" data-ga-action="abstract"> Abstract </a> </li> <li class="similar "> <a href="#similar" aria-label="navigate to Similar articles section" data-ga-category="page_nav" data-ga-action="similar"> Similar articles </a> </li> <li class="citedby "> <a href="#citedby" aria-label="navigate to Cited by section" data-ga-category="page_nav" data-ga-action="citedby"> Cited by </a> </li> <li class="publication-types "> <a href="#publication-types" aria-label="navigate to Publication types section" data-ga-category="page_nav" data-ga-action="publication-types"> Publication types </a> </li> <li class="mesh-terms "> <a href="#mesh-terms" aria-label="navigate to MeSH terms section" data-ga-category="page_nav" data-ga-action="mesh-terms"> MeSH terms </a> </li> <li class="substances "> <a href="#substances" aria-label="navigate to Substances section" data-ga-category="page_nav" data-ga-action="substances"> Substances </a> </li> <li class="related-links "> <a href="#related-links" aria-label="navigate to Related information section" data-ga-category="page_nav" data-ga-action="related-links"> Related information </a> </li> <li class="linkout "> <a href="#linkout" aria-label="navigate to LinkOut - more resources section" data-ga-category="page_nav" data-ga-action="linkout"> LinkOut - more resources </a> </li> </ul> </div> <select class="short-view" autocomplete="off" title="navigate to selected section" aria-label="Navigate to page section"> <option value="heading">Title &amp; authors</option> <option value="abstract">Abstract</option> <option value="similar">Similar articles</option> <option value="citedby">Cited by</option> <option value="publication-types">Publication types</option> <option value="mesh-terms">MeSH terms</option> <option value="substances">Substances</option> <option value="related-links">Related information</option> <option value="linkout">LinkOut - more resources</option> </select> </nav> </div> </aside> <main class="article-details" id="article-details"> <!-- "Filters applied" shows only when page is redirected from search --> <!-- because search found one result --> <header class="heading" id="heading"> <div class="full-view" id="full-view-heading"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Current biology : CB" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Current biology : CB" data-pinger-ignore> Curr Biol </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Current biology : CB"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Curr+Biol%22%5Bjour%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Curr+Biol%22%5Bjour%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&amp;journal_abbrev=Curr Biol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Curr Biol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Curr+Biol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Curr Biol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Curr Biol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Curr Biol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2002 Jun 25;12(12):983-95.</span> </div> <span class="citation-doi"> doi: 10.1016/s0960-9822(02)00895-3. </span> </div> <h1 class="heading-title"> Sonic hedgehog induces the segregation of patched and smoothened in endosomes </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Incardona+JP&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John P Incardona">John P Incardona</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Biological Structure and Center for Developmental Biology, University of Washington, Seattle 98195, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gruenberg+J&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jean Gruenberg">Jean Gruenberg</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name" href="/?term=Roelink+H&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Henk Roelink">Henk Roelink</a></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/12123571/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Department of Biological Structure and Center for Developmental Biology, University of Washington, Seattle 98195, USA.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">12123571</strong> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&amp;article_id=10.1016/s0960-9822(02)00895-3&amp;id_type=DOI" href="https://doi.org/10.1016/s0960-9822(02)00895-3" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/s0960-9822(02)00895-3 </a> </span> </li> </ul> <span class="free-label">Free article</span> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Sonic hedgehog induces the segregation of patched and smoothened in endosomes </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">John P Incardona</span><span class="citation-separator">&nbsp;et al.</span></span> </span> <span class="citation-journal"> Curr Biol<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2002">2002</time><span class="citation-separator">.</span> </span> </div> <span class="free-label">Free article</span> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/12123571/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="mobile-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> </div> <div class="extended-article-details" id="full-article-details" aria-hidden="true"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="short-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Current biology : CB" tabindex="0" aria-controls="short-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Current biology : CB" data-pinger-ignore> Curr Biol </button><div id="short-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Current biology : CB"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Curr+Biol%22%5Bjour%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Curr+Biol%22%5Bjour%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&amp;journal_abbrev=Curr Biol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Curr Biol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Curr+Biol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Curr Biol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Curr Biol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Curr Biol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2002 Jun 25;12(12):983-95.</span> </div> <span class="citation-doi"> doi: 10.1016/s0960-9822(02)00895-3. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Incardona+JP&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John P Incardona">John P Incardona</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Biological Structure and Center for Developmental Biology, University of Washington, Seattle 98195, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gruenberg+J&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jean Gruenberg">Jean Gruenberg</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name" href="/?term=Roelink+H&amp;cauthor_id=12123571" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Henk Roelink">Henk Roelink</a></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Department of Biological Structure and Center for Developmental Biology, University of Washington, Seattle 98195, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">12123571</strong> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&amp;article_id=10.1016/s0960-9822(02)00895-3&amp;id_type=DOI" href="https://doi.org/10.1016/s0960-9822(02)00895-3" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/s0960-9822(02)00895-3 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/12123571/citations/" data-citation-style="nlm" data-pubmed-format-link="/12123571/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> <strong class="sub-title"> Background: </strong> Sonic hedgehog (Shh) signal transduction involves the ligand binding Patched1 (Ptc1) protein and a signaling component, Smoothened (Smo). A select group of compounds inhibits both Shh signaling, regulated by Ptc1, and late endosomal lipid sorting, regulated by the Ptc-related Niemann-Pick C1 (NPC1) protein. This suggests that Ptc1 regulates Smo activity through a common late endosomal sorting pathway also utilized by NPC1. During signaling, Ptc accumulates in endosomal compartments, but it is unclear if Smo follows Ptc into the endocytic pathway. </p> <p> <strong class="sub-title"> Results: </strong> We characterized the dynamic subcellular distributions of Ptc1, Smo, and activated Smo mutants individually and in combination. Ptc1 and Smo colocalize extensively in the absence of ligand and are internalized together after ligand binding, but Smo becomes segregated from Ptc1/Shh complexes destined for lysosomal degradation. In contrast, activated Smo mutants do not colocalize with nor are cotransported with Ptc1. Agents that block late endosomal transport and protein sorting inhibit the ligand-induced segregation of Ptc1 and Smo. We show that, like NPC1-regulated lipid sorting, Shh signal transduction is blocked by antibodies that specifically disrupt the internal membranes of late endosomes, which provide a platform for protein and lipid sorting. </p> <p> <strong class="sub-title"> Conclusions: </strong> These data support a model in which Ptc1 inhibits Smo only when in the same compartment. Ligand-induced segregation allows Smo to signal independently of Ptc1 after becoming sorted from Ptc1/Shh complexes in the late endocytic pathway. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/10021362/" ref="article_id=10021362&amp;linksrc=similar_articles_link&amp;ordinalpos=1" data-ga-category="similar_article" data-ga-action="10021362" data-ga-label=""> Sonic hedgehog signaling by the patched-smoothened receptor complex. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Murone M, Rosenthal A, de Sauvage FJ.</span> <span class="docsum-authors short-authors">Murone M, et al.</span> <span class="docsum-journal-citation full-journal-citation">Curr Biol. 1999 Jan 28;9(2):76-84. doi: 10.1016/s0960-9822(99)80018-9.</span> <span class="docsum-journal-citation short-journal-citation">Curr Biol. 1999.</span> <span class="citation-part">PMID: <span class="docsum-pmid">10021362</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/19906846/" ref="article_id=19906846&amp;linksrc=similar_articles_link&amp;ordinalpos=2" data-ga-category="similar_article" data-ga-action="19906846" data-ga-label=""> Patched regulates Smoothened trafficking using lipoprotein-derived lipids. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Khaliullina H, Pan谩kov谩 D, Eugster C, Riedel F, Carvalho M, Eaton S.</span> <span class="docsum-authors short-authors">Khaliullina H, et al.</span> <span class="docsum-journal-citation full-journal-citation">Development. 2009 Dec;136(24):4111-21. doi: 10.1242/dev.041392. Epub 2009 Nov 11.</span> <span class="docsum-journal-citation short-journal-citation">Development. 2009.</span> <span class="citation-part">PMID: <span class="docsum-pmid">19906846</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/10504535/" ref="article_id=10504535&amp;linksrc=similar_articles_link&amp;ordinalpos=3" data-ga-category="similar_article" data-ga-action="10504535" data-ga-label=""> Expression of sonic hedgehog signal transducers, patched and smoothened, in human basal cell carcinoma. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Tojo M, Mori T, Kiyosawa H, Honma Y, Tanno Y, Kanazawa KY, Yokoya S, Kaneko F, Wanaka A.</span> <span class="docsum-authors short-authors">Tojo M, et al.</span> <span class="docsum-journal-citation full-journal-citation">Pathol Int. 1999 Aug;49(8):687-94. doi: 10.1046/j.1440-1827.1999.00938.x.</span> <span class="docsum-journal-citation short-journal-citation">Pathol Int. 1999.</span> <span class="citation-part">PMID: <span class="docsum-pmid">10504535</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/9278137/" ref="article_id=9278137&amp;linksrc=similar_articles_link&amp;ordinalpos=4" data-ga-category="similar_article" data-ga-action="9278137" data-ga-label=""> Hedgehog and its patched-smoothened receptor complex: a novel signalling mechanism at the cell surface. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Alcedo J, Noll M.</span> <span class="docsum-authors short-authors">Alcedo J, et al.</span> <span class="docsum-journal-citation full-journal-citation">Biol Chem. 1997 Jul;378(7):583-90. doi: 10.1515/bchm.1997.378.7.583.</span> <span class="docsum-journal-citation short-journal-citation">Biol Chem. 1997.</span> <span class="citation-part">PMID: <span class="docsum-pmid">9278137</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/20024066/" ref="article_id=20024066&amp;linksrc=similar_articles_link&amp;ordinalpos=5" data-ga-category="similar_article" data-ga-action="20024066" data-ga-label=""> Small-molecule modulators of the Sonic Hedgehog signaling pathway. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Stanton BZ, Peng LF.</span> <span class="docsum-authors short-authors">Stanton BZ, et al.</span> <span class="docsum-journal-citation full-journal-citation">Mol Biosyst. 2010 Jan;6(1):44-54. doi: 10.1039/b910196a. Epub 2009 Aug 27.</span> <span class="docsum-journal-citation short-journal-citation">Mol Biosyst. 2010.</span> <span class="citation-part">PMID: <span class="docsum-pmid">20024066</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed&from_uid=12123571" data-ga-category="similar_article" data-ga-action="show_all" > See all similar articles </a> </div> </div> <div class="citedby-articles" id="citedby"> <h2 class="title"> Cited by </h2> <ul class="articles-list" id="citedby-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38886055/" ref="article_id=38886055&amp;linksrc=citedby_articles_link&amp;ordinalpos=1" data-ga-category="cited_by" data-ga-action="38886055" data-ga-label=""> 尾-arrestins Are Scaffolding Proteins Required for Shh-Mediated Axon Guidance. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Sauv茅 R, Morin S, Yam PT, Charron F.</span> <span class="docsum-authors short-authors">Sauv茅 R, et al.</span> <span class="docsum-journal-citation full-journal-citation">J Neurosci. 2024 Jul 24;44(30):e0261242024. doi: 10.1523/JNEUROSCI.0261-24.2024.</span> <span class="docsum-journal-citation short-journal-citation">J Neurosci. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">38886055</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/35573667/" ref="article_id=35573667&amp;linksrc=citedby_articles_link&amp;ordinalpos=2" data-ga-category="cited_by" data-ga-action="35573667" data-ga-label=""> Sonic Hedgehog Signaling in Cerebellar Development and Cancer. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Wang W, Shiraishi R, Kawauchi D.</span> <span class="docsum-authors short-authors">Wang W, et al.</span> <span class="docsum-journal-citation full-journal-citation">Front Cell Dev Biol. 2022 Apr 29;10:864035. doi: 10.3389/fcell.2022.864035. eCollection 2022.</span> <span class="docsum-journal-citation short-journal-citation">Front Cell Dev Biol. 2022.</span> <span class="citation-part">PMID: <span class="docsum-pmid">35573667</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/35353806/" ref="article_id=35353806&amp;linksrc=citedby_articles_link&amp;ordinalpos=3" data-ga-category="cited_by" data-ga-action="35353806" data-ga-label=""> TMED2 binding restricts SMO to the ER and Golgi compartments. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Di Minin G, Holzner M, Grison A, Dumeau CE, Chan W, Monfort A, Jerome-Majewska LA, Roelink H, Wutz A.</span> <span class="docsum-authors short-authors">Di Minin G, et al.</span> <span class="docsum-journal-citation full-journal-citation">PLoS Biol. 2022 Mar 30;20(3):e3001596. doi: 10.1371/journal.pbio.3001596. eCollection 2022 Mar.</span> <span class="docsum-journal-citation short-journal-citation">PLoS Biol. 2022.</span> <span class="citation-part">PMID: <span class="docsum-pmid">35353806</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/35008597/" ref="article_id=35008597&amp;linksrc=citedby_articles_link&amp;ordinalpos=4" data-ga-category="cited_by" data-ga-action="35008597" data-ga-label=""> The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Effendi WI, Nagano T.</span> <span class="docsum-authors short-authors">Effendi WI, et al.</span> <span class="docsum-journal-citation full-journal-citation">Int J Mol Sci. 2021 Dec 24;23(1):171. doi: 10.3390/ijms23010171.</span> <span class="docsum-journal-citation short-journal-citation">Int J Mol Sci. 2021.</span> <span class="citation-part">PMID: <span class="docsum-pmid">35008597</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/34467458/" ref="article_id=34467458&amp;linksrc=citedby_articles_link&amp;ordinalpos=5" data-ga-category="cited_by" data-ga-action="34467458" data-ga-label=""> Deciphering and reconstitution of positional information in the human brain development. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Wang YF, Liu C, Xu PF.</span> <span class="docsum-authors short-authors">Wang YF, et al.</span> <span class="docsum-journal-citation full-journal-citation">Cell Regen. 2021 Sep 1;10(1):29. doi: 10.1186/s13619-021-00091-7.</span> <span class="docsum-journal-citation short-journal-citation">Cell Regen. 2021.</span> <span class="citation-part">PMID: <span class="docsum-pmid">34467458</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed_citedin&from_uid=12123571" data-ga-category="cited_by" data-ga-action="show_all" > See all "Cited by" articles </a> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Research Support, U.S. Gov&#x27;t, P.H.S." tabindex="0" aria-controls="keyword-actions-publication-types-0" aria-expanded="false" data-pinger-ignore> Research Support, U.S. Gov&#x27;t, P.H.S. </button><div id="keyword-actions-publication-types-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Research Support, U.S. Gov&#x27;t, P.H.S."><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Research+Support%2C+U.S.+Gov%27t%2C+P.H.S.%22%5Bpt%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Research+Support%2C+U.S.+Gov%27t%2C+P.H.S.%22%5Bpt%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Research Support, U.S. Gov&#x27;t, P.H.S.&quot;[pt]" data-ga-category="search" data-ga-action="pub_type" data-ga-label="Research Support, U.S. Gov&#x27;t, P.H.S."> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+U.S.+Gov%27t%2C+P.H.S." data-ga-category="search_mesh" data-ga-action="pub_type_link" data-ga-label="Research Support, U.S. Gov&#x27;t, P.H.S."> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Research Support, U.S. Gov&#x27;t, P.H.S.&quot;[pt]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Research Support, U.S. Gov&#x27;t, P.H.S.&quot;[pt]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="mesh-terms" class="mesh-terms keywords-section"> <h2 class="title"> MeSH terms </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Animals" tabindex="0" aria-controls="keyword-actions-mesh-terms-0" aria-expanded="false" data-pinger-ignore> Animals </button><div id="keyword-actions-mesh-terms-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Animals"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Animals%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Animals%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Animals&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Animals"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Animals" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Animals"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Animals&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Animals&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Biological Transport" tabindex="0" aria-controls="keyword-actions-mesh-terms-1" aria-expanded="false" data-pinger-ignore> Biological Transport </button><div id="keyword-actions-mesh-terms-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Biological Transport"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Biological+Transport%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Biological+Transport%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Biological Transport&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Biological Transport"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Biological+Transport" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Biological Transport"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Biological Transport&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Biological Transport&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Cell Line" tabindex="0" aria-controls="keyword-actions-mesh-terms-2" aria-expanded="false" data-pinger-ignore> Cell Line </button><div id="keyword-actions-mesh-terms-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Cell Line"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Cell+Line%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Cell+Line%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Cell Line&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Cell Line"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Cell Line"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Cell Line&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Cell Line&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Drosophila" tabindex="0" aria-controls="keyword-actions-mesh-terms-3" aria-expanded="false" data-pinger-ignore> Drosophila </button><div id="keyword-actions-mesh-terms-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Drosophila"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Drosophila%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Drosophila%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Drosophila&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Drosophila"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Drosophila" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Drosophila"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Drosophila&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Drosophila&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Drosophila Proteins*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-4" aria-expanded="false" data-pinger-ignore> Drosophila Proteins* </button><div id="keyword-actions-mesh-terms-major-4" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Drosophila Proteins*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Drosophila+Proteins%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Drosophila+Proteins%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Drosophila Proteins&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Drosophila Proteins*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Drosophila+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Drosophila Proteins*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Drosophila Proteins&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Drosophila Proteins&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Endosomes / physiology*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-5" aria-expanded="false" data-pinger-ignore> Endosomes / physiology* </button><div id="keyword-actions-mesh-terms-major-5" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Endosomes / physiology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Endosomes%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Endosomes%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Endosomes/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Endosomes / physiology*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Endosomes" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Endosomes / physiology*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Endosomes/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Endosomes/physiology&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Hedgehog Proteins" tabindex="0" aria-controls="keyword-actions-mesh-terms-6" aria-expanded="false" data-pinger-ignore> Hedgehog Proteins </button><div id="keyword-actions-mesh-terms-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Hedgehog Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Hedgehog+Proteins%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Hedgehog+Proteins%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Hedgehog Proteins&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Hedgehog Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Hedgehog+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Hedgehog Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Hedgehog Proteins&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Hedgehog Proteins&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Membrane Proteins / physiology*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-7" aria-expanded="false" data-pinger-ignore> Membrane Proteins / physiology* </button><div id="keyword-actions-mesh-terms-major-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Membrane Proteins / physiology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Membrane+Proteins%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Membrane+Proteins%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Membrane Proteins/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Membrane Proteins / physiology*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Membrane+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Membrane Proteins / physiology*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Membrane Proteins/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Membrane Proteins/physiology&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Patched Receptors" tabindex="0" aria-controls="keyword-actions-mesh-terms-8" aria-expanded="false" data-pinger-ignore> Patched Receptors </button><div id="keyword-actions-mesh-terms-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Patched Receptors"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Patched+Receptors%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Patched+Receptors%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Patched Receptors&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Patched Receptors"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Patched+Receptors" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Patched Receptors"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Patched Receptors&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Patched Receptors&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Receptors, Cell Surface / physiology*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-9" aria-expanded="false" data-pinger-ignore> Receptors, Cell Surface / physiology* </button><div id="keyword-actions-mesh-terms-major-9" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, Cell Surface / physiology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+Cell+Surface%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Receptors%2C+Cell+Surface%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Receptors, Cell Surface/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Receptors, Cell Surface / physiology*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Receptors%2C+Cell+Surface" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Receptors, Cell Surface / physiology*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Receptors, Cell Surface/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Receptors, Cell Surface/physiology&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Receptors, G-Protein-Coupled*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-10" aria-expanded="false" data-pinger-ignore> Receptors, G-Protein-Coupled* </button><div id="keyword-actions-mesh-terms-major-10" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, G-Protein-Coupled*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+G-Protein-Coupled%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Receptors%2C+G-Protein-Coupled%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Receptors, G-Protein-Coupled&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Receptors, G-Protein-Coupled*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Receptors%2C+G-Protein-Coupled" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Receptors, G-Protein-Coupled*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Receptors, G-Protein-Coupled&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Receptors, G-Protein-Coupled&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Signal Transduction" tabindex="0" aria-controls="keyword-actions-mesh-terms-11" aria-expanded="false" data-pinger-ignore> Signal Transduction </button><div id="keyword-actions-mesh-terms-11" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Signal Transduction"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Signal+Transduction%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Signal+Transduction%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Signal Transduction&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Signal Transduction"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Signal+Transduction" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Signal Transduction"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Signal Transduction&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Signal Transduction&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Smoothened Receptor" tabindex="0" aria-controls="keyword-actions-mesh-terms-12" aria-expanded="false" data-pinger-ignore> Smoothened Receptor </button><div id="keyword-actions-mesh-terms-12" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Smoothened Receptor"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Smoothened+Receptor%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Smoothened+Receptor%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Smoothened Receptor&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Smoothened Receptor"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Smoothened+Receptor" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Smoothened Receptor"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Smoothened Receptor&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Smoothened Receptor&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Trans-Activators / physiology*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-13" aria-expanded="false" data-pinger-ignore> Trans-Activators / physiology* </button><div id="keyword-actions-mesh-terms-major-13" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Trans-Activators / physiology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Trans-Activators%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Trans-Activators%2Fphysiology%22%5BMAJR%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Trans-Activators/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Trans-Activators / physiology*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Trans-Activators" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Trans-Activators / physiology*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Trans-Activators/physiology&quot;[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Trans-Activators/physiology&quot;[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Vertebrates" tabindex="0" aria-controls="keyword-actions-mesh-terms-14" aria-expanded="false" data-pinger-ignore> Vertebrates </button><div id="keyword-actions-mesh-terms-14" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Vertebrates"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Vertebrates%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Vertebrates%22%5BMeSH%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Vertebrates&quot;[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Vertebrates"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Vertebrates" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Vertebrates"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Vertebrates&quot;[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Vertebrates&quot;[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Drosophila Proteins" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> Drosophila Proteins </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Drosophila Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Drosophila+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Drosophila+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Drosophila Proteins&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Drosophila Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Drosophila+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Drosophila Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Drosophila Proteins&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Drosophila Proteins&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Hedgehog Proteins" tabindex="0" aria-controls="keyword-actions-substances-1" aria-expanded="false" data-pinger-ignore> Hedgehog Proteins </button><div id="keyword-actions-substances-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Hedgehog Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Hedgehog+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Hedgehog+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Hedgehog Proteins&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Hedgehog Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Hedgehog+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Hedgehog Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Hedgehog Proteins&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Hedgehog Proteins&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Membrane Proteins" tabindex="0" aria-controls="keyword-actions-substances-2" aria-expanded="false" data-pinger-ignore> Membrane Proteins </button><div id="keyword-actions-substances-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Membrane Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Membrane+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Membrane+Proteins%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Membrane Proteins&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Membrane Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Membrane+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Membrane Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Membrane Proteins&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Membrane Proteins&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Patched Receptors" tabindex="0" aria-controls="keyword-actions-substances-3" aria-expanded="false" data-pinger-ignore> Patched Receptors </button><div id="keyword-actions-substances-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Patched Receptors"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Patched+Receptors%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Patched+Receptors%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Patched Receptors&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Patched Receptors"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Patched+Receptors%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Patched Receptors"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Patched Receptors&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Patched Receptors&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Receptors, Cell Surface" tabindex="0" aria-controls="keyword-actions-substances-4" aria-expanded="false" data-pinger-ignore> Receptors, Cell Surface </button><div id="keyword-actions-substances-4" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, Cell Surface"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+Cell+Surface%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Receptors%2C+Cell+Surface%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Receptors, Cell Surface&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Receptors, Cell Surface"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Receptors%2C+Cell+Surface%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Receptors, Cell Surface"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Receptors, Cell Surface&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Receptors, Cell Surface&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Receptors, G-Protein-Coupled" tabindex="0" aria-controls="keyword-actions-substances-5" aria-expanded="false" data-pinger-ignore> Receptors, G-Protein-Coupled </button><div id="keyword-actions-substances-5" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, G-Protein-Coupled"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+G-Protein-Coupled%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Receptors%2C+G-Protein-Coupled%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Receptors, G-Protein-Coupled&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Receptors, G-Protein-Coupled"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Receptors%2C+G-Protein-Coupled%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Receptors, G-Protein-Coupled"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Receptors, G-Protein-Coupled&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Receptors, G-Protein-Coupled&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Smoothened Receptor" tabindex="0" aria-controls="keyword-actions-substances-6" aria-expanded="false" data-pinger-ignore> Smoothened Receptor </button><div id="keyword-actions-substances-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Smoothened Receptor"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Smoothened+Receptor%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Smoothened+Receptor%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Smoothened Receptor&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Smoothened Receptor"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Smoothened+Receptor%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Smoothened Receptor"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Smoothened Receptor&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Smoothened Receptor&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Trans-Activators" tabindex="0" aria-controls="keyword-actions-substances-7" aria-expanded="false" data-pinger-ignore> Trans-Activators </button><div id="keyword-actions-substances-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Trans-Activators"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Trans-Activators%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22Trans-Activators%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Trans-Activators&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Trans-Activators"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Trans-Activators%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Trans-Activators"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;Trans-Activators&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;Trans-Activators&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword smo protein, Drosophila" tabindex="0" aria-controls="keyword-actions-substances-8" aria-expanded="false" data-pinger-ignore> smo protein, Drosophila </button><div id="keyword-actions-substances-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword smo protein, Drosophila"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22smo+protein%2C+Drosophila%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" data-href="/?term=%22smo+protein%2C+Drosophila%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;smo protein, Drosophila&quot;[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="smo protein, Drosophila"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22smo+protein%2C+Drosophila%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="smo protein, Drosophila"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term="&quot;smo protein, Drosophila&quot;[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label="&quot;smo protein, Drosophila&quot;[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="related-links" class="related-links"> <h2 class="title"> Related information </h2> <ul class="related-links-list"><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&amp;from_uid=12123571" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=12123571&ordinalpos=1&linkpos=1"> Gene </a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&amp;from_uid=12123571" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=12123571&ordinalpos=1&linkpos=2"> Protein (RefSeq) </a></li></ul> </div> <div id="linkout" class="linkout"> <h2 class="title"> LinkOut - more resources </h2> <ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a href="https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(02)00895-3" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3048&uid=12123571&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=9107782" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="Elsevier Science" > Elsevier Science </a></li></ul></li><li><h3 class="linkout-category">Other Literature Sources</h3><ul class="linkout-category-links"><li><a href="https://facultyopinions.com/pubmed/12123571" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3533&uid=12123571&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=9107782" data-ga-category="link_out" data-ga-action="Other Literature Sources" data-ga-label="H1 Connect" > H1 Connect </a></li></ul></li><li><h3 class="linkout-category">Miscellaneous</h3><ul class="linkout-category-links"><li><a href="https://assays.cancer.gov/non-CPTAC-3385" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=8855&uid=12123571&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=9107782" data-ga-category="link_out" data-ga-action="Miscellaneous" data-ga-label="NCI CPTAC Assay Portal" > NCI CPTAC Assay Portal </a></li></ul></li></ul> </div> </main> <div class="overlay" role="dialog" aria-label="Full Text Links Dialog"> <div id="full-text-links-dialog" class="dialog full-text-links-dialog"> <strong class="title">Full text links</strong> <button class="close-overlay" tabindex="2">[x]</button> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(02)00895-3" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=12123571&amp;db=pubmed&amp;nlmid=9107782" title="See full text options at Elsevier Science" tabindex="1" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="12123571" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="full text provider logo"><span class="text"> Elsevier Science </span></a> </div> </div> </div> <div class="overlay" role="dialog" aria-label="Citation Dialog"> <div class="dialog citation-dialog"> <button class="close-overlay" tabindex="1">[x]</button> <div class="title">Cite</div> <div class="citation-text-block"> <div class="citation-text"></div> <div class="citation-actions"> <button class="copy-button dialog-focus" data-ga-category="save_share" data-ga-action="cite" data-ga-label="copy" tabindex="2"> Copy </button> <form method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="GdCJcD0KrnNcDiLotPJjmYXIgTOEJTMKjtKv11nP6f5woBxPGPZ0gc6reXqeDRuC"> <button type="submit" class="export-button" data-ga-category="save_share" data-ga-action="cite" data-ga-label="download" title="Download a file for external citation management software" tabindex="3"> <span class="download-title">Download .nbib</span> <span class="download-title-mobile">.nbib</span> </button> </form> <div class="citation-style-selector-wrapper"> <label class="selector-label">Format:</label> <select aria-label="Format" class="citation-style-selector" tabindex="4"> <option data-style-url-name="ama" value="AMA" > AMA </option> <option data-style-url-name="apa" value="APA" > APA </option> <option data-style-url-name="mla" value="MLA" > MLA </option> <option data-style-url-name="nlm" value="NLM" selected="selected"> NLM </option> </select> </div> </div> </div> </div> </div> <div class="overlay" role="dialog" aria-label="More Actions Dialog"> <div id="more-actions-dialog" class="dialog more-actions-dialog"> <strong class="title">Send To</strong> <ul class="more-actions-links"> <li><a id="clipboard-trigger" role="button" class="submit-button clipboard-trigger clipboard-trigger-target dialog-focus link-item " href="#">Clipboard</a></li> <li><a class="email-trigger link-item" role="button" href="#">Email</a></li> <li><a class="save-trigger link-item" role="button" href="#">Save</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F%23open-bibliography-panel">My Bibliography</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F%23open-collections-panel">Collections</a></li> <li><a class="citation-manager-trigger link-item" role="button" href="#">Citation Manager</a></li> </ul> <button class="close-overlay">[x]</button> </div> </div> </div> <div id="ncbi-footer"> <div class="literature-footer" role="complementary" title="Links to NCBI Literature Resources"> <div class="usa-grid"> <p class="literature-footer-text">NCBI Literature Resources</p> <p class="literature-footer-text"> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh/">MeSH</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="pmc_link" href="https://www.ncbi.nlm.nih.gov/pmc/">PMC</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="bookshelf_link" href="https://www.ncbi.nlm.nih.gov/books">Bookshelf</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="disclaimer_link" href="/disclaimer/">Disclaimer</a> </p> <p class="literature-footer-text attribution-statement">The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.</p> </div> </div> <!-- ========== BEGIN FOOTER ========== --> <footer> <section class="icon-section"> <div id="icon-section-header" class="icon-section_header">Follow NCBI</div> <div class="grid-container container"> <div class="icon-section_container"> <a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"> <svg width="40" height="40" viewBox="0 0 40 37" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1008"> <path id="path1008" d="M6.06736 7L16.8778 20.8991L6.00001 32.2H10.2L18.6 23.1L25.668 32.2H34L22.8 17.5L31.9 7H28.4L20.7 15.4L14.401 7H6.06898H6.06736ZM9.66753 8.73423H12.9327L29.7327 30.4658H26.5697L9.66753 8.73423Z" fill="#5B616B"/> </g> </svg> </a> <a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>Facebook</title> <path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z"> </path> </svg></a> <a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>LinkedIn</title> <path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z"> </path> </svg></a> <a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <defs> <style> .cls-11, .cls-12 { fill: #737373; } .cls-11 { fill-rule: evenodd; } </style> </defs> <title>GitHub</title> <path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z"> </path> <path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1"> </path> <path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08"> </path> <path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path> <path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0"> </path> <path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0"> </path> <path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0"> </path> <path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path> </svg></a> <a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog"> <svg id="Layer_1" data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 40"><defs><style>.cls-1{fill:#737373;}</style></defs><path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"/></svg> </a> </div> </div> </section> <section class="container-fluid bg-primary"> <div class="container pt-5"> <div class="row mt-3"> <div class="col-lg-3 col-12"> <p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p> <ul class="list-inline social_media"> <li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"> <svg width="35" height="35" viewBox="0 0 38 35" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1009" clip-path="url(#clip0_65276_3946)"> <path id="Vector" d="M17.5006 34.6565C26.9761 34.6565 34.6575 26.9751 34.6575 17.4996C34.6575 8.02416 26.9761 0.342773 17.5006 0.342773C8.02514 0.342773 0.34375 8.02416 0.34375 17.4996C0.34375 26.9751 8.02514 34.6565 17.5006 34.6565Z" fill="#205493" stroke="white" stroke-width="1.2" stroke-miterlimit="10"></path> <path id="path1009" d="M8.54811 8.5L16.2698 18.4279L8.50001 26.5H11.5L17.5 20L22.5486 26.5H28.5L20.5 16L27 8.5H24.5L19 14.5L14.5007 8.5H8.54927H8.54811ZM11.1197 9.73873H13.4519L25.4519 25.2613H23.1926L11.1197 9.73873Z" fill="white"></path> </g> <defs> <clipPath id="clip0_65276_3946"> <rect width="38" height="38" fill="white"></rect> </clipPath> </defs> </svg></a> </li> <li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank"> <svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <style type="text/css"> .st10 { fill: #FFFFFF; } .st110 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } </style> <title>SM-Facebook</title> <g> <g> <path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path> </g> </g> <circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle> </svg> </a></li> <li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <title>SM-Youtube</title> <style type="text/css"> .st4 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } .st5 { fill: #FFFFFF; } </style> <circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle> <g transform="translate(0,-952.36218)"> <path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path> </g> </svg></a></li> </ul> </div> <div class="col-lg-3 col-12"> <p class="address_footer text-white">National Library of Medicine<br> <a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br> Bethesda, MD 20894</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br> <a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br> <a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br> <a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br> <a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p> </div> </div> <div class="row"> <div class="col-lg-12 centered-lg"> <nav class="bottom-links"> <ul class="mt-3"> <li> <a class="text-white" href="//www.nlm.nih.gov/">NLM</a> </li> <li> <a class="text-white" href="https://www.nih.gov/">NIH</a> </li> <li> <a class="text-white" href="https://www.hhs.gov/">HHS</a> </li> <li> <a class="text-white" href="https://www.usa.gov/">USA.gov</a> </li> </ul> </nav> </div> </div> </div> </section> </footer> <!-- ========== END FOOTER ========== --> <!-- javascript to inject NWDS meta tags. Note: value of nwds_version is updated by "npm version" command --> <script type="text/javascript"> var nwds_version = "1.2.3"; var meta_nwds_ver = document.createElement('meta'); meta_nwds_ver.name = 'ncbi_nwds_ver'; meta_nwds_ver.content = nwds_version; document.getElementsByTagName('head')[0].appendChild(meta_nwds_ver); var meta_nwds = document.createElement('meta'); meta_nwds.name = 'ncbi_nwds'; meta_nwds.content = 'yes'; document.getElementsByTagName('head')[0].appendChild(meta_nwds); var alertsUrl = "/core/alerts/alerts.js"; if (typeof ncbiBaseUrl !== 'undefined') { alertsUrl = ncbiBaseUrl + alertsUrl; } </script> </div> <!-- jQuery with plugins --> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/js/output.293fbf76aa18.js"></script> <!-- Project base scripts --> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/js/output.550e9c8906a2.js"></script> <script> ncbi.awesome.basePage.init({ userInfo: { isLoggedIn: false, username: "", loginUrl: "https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12123571%2F", logoutUrl: "https://www.ncbi.nlm.nih.gov/account/signout/?back_url=https%3A//pubmed.ncbi.nlm.nih.gov/12123571/" }, baseUrl: 'https://www.ncbi.nlm.nih.gov', noSessionCookieName: "pm-ns", searchIdCookieName: "pm-sid", adjNavSearchIdCookieName: "pm-adjnav-sid", searchFormSubmittedCookieName: "pm-sfs", isOnSearchPageCookieName: "pm-iosp", backToSearchCookieName: "pm-btsl", clinicalSeeAllCookieName: "pm-csa", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", userShareRequestFailed: "", noSharedSettings: "myncbi_no_shared_settings", noSharedAccount: "myncbi_no_shared_account" }); </script> <script type="module"> import dismissableNCBIAlert from "https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/core/dismissable-ncbi-alert.js"; jQuery.getScript("https://www.ncbi.nlm.nih.gov/core/alerts/alerts.js", function () { galert(['body > *:last-child']); dismissableNCBIAlert(); }).fail(function() { }); </script> <script defer type="text/javascript" src="https://cdn.ncbi.nlm.nih.gov/core/pinger/pinger.js"> </script> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/CACHE/js/output.04d45d85d031.js"></script> <script> ncbi.awesome.articlePage.init({ baseSuggestionsUrl: "/suggestions/", mathJaxUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/mathjax/unpacked/MathJax.js?config=MML_CHTML", clipboardAPIRoot: "/ajax/clipboard/", clipboardNextPageUrl: "/clipboard-next-page/", searchIdCookieName: "pm-sid", searchFormSubmittedCookieName: "pm-sfs", backToSearchCookieName: "pm-btsl", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", longTermPrefix: "longquery", adjNavURLPath: "/12123571/adj-nav/", adjNavSearchIdCookieName: "pm-adjnav-sid", articlePageUrl: "/12123571/", markJSUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/ed1a5a1f-b279-475e-88e3-75f261729818/mark.js/dist/jquery.mark.js", termHighlightColor: "", highlightedTokens: "", citeFormatPreferenceCookieName: "pm-cf" }); </script> </body> </html>

Pages: 1 2 3 4 5 6 7 8 9 10