Phosphoinositide Pathway | Cell Signaling Technology

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Signaling</h1> </div> <div id="pathway-wrapper"> <span id="pathway-copyright"> © Cell Signaling Technology. All Rights Reserved.</span> <div id="cst-wrapper" class="text-center"> <div class="wrapper-parent"> <div class="wrapper" style="position:relative"> <div id="pathway-node-container"> <object data="https://media.cellsignal.com/www/scalable-pathways/svg/Phosphoinositide Signaling-test.svg" id="pathways-window" name="pathways-window" type="image/svg+xml"><img alt="Phosphoinositide (Lipid) Signaling" src="https://media.cellsignal.com/www/scalable-pathways/svg/Phosphoinositide Signaling-test.svg" /></object><div class="overlay"> <div class="overlay-button"> <button class="btn btn-primary btn-block">VIEW INTERACTIVE PATHWAY</button> </div> </div> </div> <div class="pathway-buttons desktop" id="pathway-buttons" > <div><i class="cstf cstf-arrow-left"></i></div> <div><i class="cstf cstf-arrows-alt"></i></div> <div><i class="cstf cstf-minus"></i></div> <div><i class="cstf cstf-plus"></i></div> </div> </div> </div> </div> <div class="text-center" style="margin-top: 15px;"> <a target="_blank" href="https://media.cellsignal.com/www/pdfs/science/pathways/phosphoinositide-lipid-signaling.pdf" class="btn download-pathway-btn">DOWNLOAD PATHWAY</a> </div> <div data-template="content-pathway-diagram-legend"> <ul class="nav nav-tabs" role="tablist"> <li class="nav-item active" id="description-tab" data-toggle="tab" href="#description" role="tab" aria-controls="description" aria-selected="true"> <a class="nav-link active in"> Pathway Description </a> </li> <li class="nav-item" id="legend-tab" data-toggle="tab" href="#legend" role="tab" aria-controls="legend" aria-selected="false"> <a class="nav-link">Legend</a> </li> </ul> <div class="tab-content"> <div class="tab-pane fade active in" id="description" role="tabpanel" aria-labelledby="description-tab"> <div class="row"> <div class="col-md-8"> <div id="cst-pathway-text-wrapper"><h2 id="describe">Pathway Description:</h2> <p class="p-empty">Phosphatidylinositol (PtdIns) is a small lipid molecule composed of an inositol ring and two fatty acid chains connected through a glycerol backbone, a structure that allows PtdIns to anchor on the cytoplasmic face of cellular membranes. PtdIns is phosphorylated by a host of lipid kinases at the 3, 4, and/or 5 hydroxyl positions of the inositol ring, producing a variety of phosphatidylinositol monophosphates (PI3P, PI4P, and PI5P), diphosphates [PI(3,4)P<sub>2</sub>, PI(3,5)P<sub>2</sub>, PI(4,5)P<sub>2</sub>], and a triphosphate [PI(3,4,5)P<sub>3</sub>] that are collectively known as phosphoinositides. The phosphorylations are removed by site-specific lipid phosphatases, enabling dynamic flux between lipid phosphorylation states. In general, phosphatidylinositol monophosphates are localized to intracellular membranes (endocytic vesicles, golgi apparatus, nucleus), while di- and triphosphates are found at the plasma membrane. PtdIns (synthesized at the endoplasmic reticulum) and phosphoinositides shuttle among various subcellular compartments by intracellular vesicles that enable association with their corresponding modifying enzymes. Phosphoinositides are universal signaling entities that regulate cell activities through direct interaction with membrane proteins (e.g., ion channels, GPCRs) or through membrane recruitment of cytosolic proteins containing domains that directly bind phosphoinositides, such as pleckstrin homology (PH), FYVE, WD40 repeats, FERM, PTB, and PDZ domains, among others. By far the best studied phosphoinositide is PI(3,4,5)P<sub>3</sub>, which is synthesized from PI(4,5)P<sub>2</sub> by PI3K Class I and dephosphorylated by PTEN. Both PI3K Class I and PTEN are central mediators of receptor tyrosine kinase-induced Akt signaling, and are often mutated in many forms of cancer. In addition to its effect on cell proliferation, survival, and metabolism associated with Akt signaling, phosphoinositide signaling also induces cytoskeletal changes and actin remodeling, and plays a role in clathrin-mediated endocytosis, vesicle trafficking, membrane dynamics, autophagy, cell division/cytokinesis, cell migration, and UV stress response.</p></div><div id="cst-pathway-reviews-wrapper"><h2 id="reviews">Selected Reviews:</h2> <ul> <li>Balla T (2013) <a href="http://www.ncbi.nlm.nih.gov/pubmed/23899561" target="new">Phosphoinositides: tiny lipids with giant impact on cell regulation.</a> <cite>Physiol. Rev.</cite> 93(3), 1019–137.</li> <li>Hammond GR, Balla T (2015) <a href="http://www.ncbi.nlm.nih.gov/pubmed/25732852" target="new">Polyphosphoinositide binding domains: Key to inositol lipid biology.</a> <cite>Biochim. Biophys. Acta</cite> 1851(6), 746–58.</li> <li>Lystad AH, Simonsen A (2016) <a href="http://www.ncbi.nlm.nih.gov/pubmed/27391591" target="new">Phosphoinositide-binding proteins in autophagy.</a> <cite>FEBS Lett.</cite> 590(15), 2454–68.</li> <li>Marat AL, Haucke V (2016) <a href="http://www.ncbi.nlm.nih.gov/pubmed/26888746" target="new">Phosphatidylinositol 3-phosphates-at the interface between cell signalling and membrane traffic.</a> <cite>EMBO J.</cite> 35(6), 561–79.</li> <li>Cauvin C, Echard A (2015) <a href="http://www.ncbi.nlm.nih.gov/pubmed/25449648" target="new">Phosphoinositides: Lipids with informative heads and mastermind functions in cell division.</a> <cite>Biochim. Biophys. Acta</cite> 1851(6), 832–43.</li> <li>Wang W, Lv J, Wang L, Wang X, Ye L (2017) <a href="http://www.ncbi.nlm.nih.gov/pubmed/27582428" target="new">The impact of heterogeneity in phosphoinositide 3-kinase pathway in human cancer and possible therapeutic treatments.</a> <cite>Semin. Cell Dev. Biol.</cite> 64, 116–124.</li> </ul> <div class="revision">created August 2017</div></div></div> <div class="col-md-4"> <div class="description-links"> <p> <a href="/common/content/content.jsp?id=science-pathways-permission"> Request Permission for Pathway </a> </p> <p> <a target="_blank" id="pathway_pdf" href="https://media.cellsignal.com/www/pdfs/science/pathways/phosphoinositide-lipid-signaling.pdf">View PDF</a> </p> </div> </div> </div> </div> <div class="tab-pane fade" id="legend" role="tabpanel" aria-labelledby="legend-tab"> <style type="text/css">.legend-text { margin-top:6px; } </style> <div class="container-fluid"> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Acetylase" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/acetylase.svg" width="45" /></div> <div class="col-md-5 legend-text">Acetylase</div> <div class="col-md-1 pictogram-image"><img alt="Metabolic Enzyme" height="35" 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legend-text">Apoptosis/Autophagy Regulator</div> <div class="col-md-1 pictogram-image"><img alt="Phosphatase" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/phospatase.svg" width="45" /></div> <div class="col-md-5 legend-text">Phosphatase</div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Cell Cycle Regulator" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/cell-cycle-regulator.svg" width="45" /></div> <div class="col-md-5 legend-text">Cell Cycle Regulator</div> <div class="col-md-1 pictogram-image"><img alt="Protein Complex" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/protein-complex.svg" width="45" /></div> <div class="col-md-5 legend-text">Protein Complex</div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Deacetylase or Cytoskeletal Protein" height="35" 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src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/transcription-factor.svg" width="45" /></div> <div class="col-md-5 legend-text">Transcription Factor or Translation Factor</div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="GTPase/GAP/GEF" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/gt-pase.svg" width="45" /></div> <div class="col-md-5 legend-text">GTPase/GAP/GEF</div> <div class="col-md-1 pictogram-image"><img alt="Receptor" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/receptor.svg" width="45" /></div> <div class="col-md-5 legend-text">Receptor</div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Kinase" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/kinase.svg" width="45" /></div> <div class="col-md-5 legend-text">Kinase</div> <div class="col-md-1 pictogram-image"><img alt="Other" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/other.svg" width="45" /></div> <div class="col-md-5 legend-text">Other</div> </div> <div class="row"> <div class="col-md-12"> <div class="legend-separator"> </div> </div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Direct Process" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/direct-process.svg" width="45" /></div> <div class="col-md-5 legend-text">Direct Process</div> <div class="col-md-1 pictogram-image"><img alt="Tentative Process" height="35" src="https://media.cellsignal.com/www/images/science/pathways/pathway-legend/svg/tentative-process.svg" width="45" /></div> <div class="col-md-5 legend-text">Tentative Process</div> </div> <div class="row legend1"> <div class="col-md-1 pictogram-image"><img alt="Translocation Process" height="35" 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