View source for Biology:PI(4,5)P2 Cycle

The '''PI(4,5)P<sub>2</sub> cycle''' or simply '''PIP<sub>2</sub> cycle''' (also known as '''PI cycle''' in past) is one of the important signalling cascades underlying many cellular functions including GPCR signaling, [[Biology:Cytokinesis|cytokinesis]],<ref>{{cite journal|title=Regulation of the actin cytoskeleton by PIP2 in cytokinesis|first1=Michael R.|last1=Logan|first2=Craig A.|last2=Mandato|date=1 June 2006|journal=Biology of the Cell|volume=98|issue=6|pages=377–388|doi=10.1042/BC20050081|pmid=16704377|s2cid=37783775 |doi-access=free}}</ref> [[Biology:Endocytosis|endocytosis]],<ref>{{cite journal|title=The functions of anionic phospholipids during clathrin-mediated endocytosis site initiation and vesicle formation|first1=Yidi|last1=Sun|first2=David G.|last2=Drubin|date=15 December 2012|journal=Journal of Cell Science|volume=125|issue=Pt 24|pages=6157–6165|doi=10.1242/jcs.115741|pmid=23097040|pmc=3585524}}</ref> and [[Biology:Apoptosis|apoptosis]].<ref>{{cite journal|title=Regulation of apoptosis by phosphatidylinositol 4,5-bisphosphate inhibition of caspases, and caspase inactivation of phosphatidylinositol phosphate 5-kinases|first1=M.|last1=Mejillano|first2=M.|last2=Yamamoto|first3=A. L.|last3=Rozelle|first4=H. Q.|last4=Sun|first5=X.|last5=Wang|first6=H. L.|last6=Yin|date=19 January 2001|journal=The Journal of Biological Chemistry|volume=276|issue=3|pages=1865–1872|doi=10.1074/jbc.M007271200|pmid=11042212|doi-access=free}}</ref>
== Signalling steps ==

[[File:PIP2 Cycle.png|thumb|General PI(4,5)P2 cycle]]
PIP<sub>2</sub> cycle involves steps of chemical reactions characterized by various enzymes. First hydrolysis of PIP<sub>2</sub> molecules by activated [[Biology:Phospholipase C|phospholipase C]] leads to formation of diacylglycerol and [[Chemistry:Inositol trisphosphate|inositol trisphosphate]]. These two are themselves important second messengers.<ref>{{cite journal|title=IP3 receptor/Ca2+ channel: from discovery to new signaling concepts|first=Katsuhiko|last=Mikoshiba|date=1 September 2007|journal=Journal of Neurochemistry|volume=102|issue=5|pages=1426–1446|doi=10.1111/j.1471-4159.2007.04825.x|pmid=17697045|s2cid=4242836 }}</ref> Diacylglycerol further converted into [[Biology:Phosphatidic acid|phosphatidic acid]] (PA) by [[Biology:Diacylglycerol kinase|DAGK]] enzyme. Furthermore, CDP-diacylglycerol synthetase uses [[Chemistry:Cytidine diphosphate|CTP]] to create cytidine diphosphate diacylglycerol from PA.<ref>{{cite web|url=https://www.lipidmaps.org/resources/lipidweb/lipidweb_html/lipids/complex/cdp-dg/index.htm|title=Cytidine Diphosphate Diacylglycerol (CDP-DAG), phospholipid biosynthesis - composition and biochemistry|first=William (Bill) W.|last=Christie|website=www.lipidhome.co.uk|access-date=19 July 2021}}</ref><ref>{{cite journal|title=CDP-Diacylglycerol Synthetase Coordinates Cell Growth and Fat Storage through Phosphatidylinositol Metabolism and the Insulin Pathway|first1=Yuan|last1=Liu|first2=Wei|last2=Wang|first3=Guanghou|last3=Shui|first4=Xun|last4=Huang|date=6 March 2014|journal=PLOS Genetics|volume=10|issue=3|pages=e1004172|doi=10.1371/journal.pgen.1004172|pmid=24603715 |pmc=3945474 |doi-access=free }}</ref> Generated CDP-DAG then condensed to [[Chemistry:Phosphatidylinositol|PI]] by phosphatidylinositol synthase.<ref>{{cite journal|title=Phosphatidylinositol Synthase and Diacylglycerol Platforms Bust a Move|first1=Vytas A.|last1=Bankaitis|first2=Aby|last2=Grabon|date=15 November 2011|journal=Developmental Cell|volume=21|issue=5|pages=810–812|doi=10.1016/j.devcel.2011.10.016|pmid=22075144|pmc=3242638}}</ref> This PI is then phosphorylated to [[Biology:Phosphatidylinositol 4-phosphate|PI4P]] and back to PIP<sub>2</sub> via action of PI4K and PIP5K<ref>{{cite journal|url=http://jcs.biologists.org/content/122/21/3837|title=PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions|first1=Iman van den|last1=Bout|first2=Nullin|last2=Divecha|date=1 November 2009|journal=J Cell Sci|volume=122|issue=21|pages=3837–3850|access-date=3 August 2017|via=jcs.biologists.org|doi=10.1242/jcs.056127|pmid=19889969|s2cid=25453017 |doi-access=}}</ref>

== References ==
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[[Category:Cell signaling]]

{{Sourceattribution|PI(4,5)P2 Cycle}}