The PI(4,5)P2 cycle or simply PIP2 cycle (also known as PI cycle in past) is one of the important signalling cascades underlying many cellular functions including GPCR signaling , cytokinesis ,[ 1] endocytosis ,[ 2] apoptosis .[ 3]
Signalling steps
General PI(4,5)P2 cycle PIP2 cycle involves steps of chemical reactions characterized by various enzymes. First hydrolysis of PIP2 molecules by activated phospholipase C leads to formation of diacylglycerol and inositol trisphosphate . These two are themselves important second messengers.[ 4] phosphatidic acid (PA) by DAGK enzyme. Furthermore, CDP-diacylglycerol synthetase uses CTP to create cytidine diphosphate diacylglycerol from PA.[ 5] [ 6] PI by phosphatidylinositol synthase.[ 7] PI4P and back to PIP2 via action of PI4K and PIP5K[ 8]
References
^ Logan, Michael R.; Mandato, Craig A. (1 June 2006). "Regulation of the actin cytoskeleton by PIP2 in cytokinesis" . Biology of the Cell . 98 (6): 377– 388. doi :10.1042/BC20050081 PMID 16704377 . S2CID 37783775 . ^ Sun, Yidi; Drubin, David G. (15 December 2012). "The functions of anionic phospholipids during clathrin-mediated endocytosis site initiation and vesicle formation" . Journal of Cell Science . 125 (Pt 24): 6157– 6165. doi :10.1242/jcs.115741 . PMC 3585524 PMID 23097040 . ^ Mejillano, M.; Yamamoto, M.; Rozelle, A. L.; Sun, H. Q.; Wang, X.; Yin, H. L. (19 January 2001). "Regulation of apoptosis by phosphatidylinositol 4,5-bisphosphate inhibition of caspases, and caspase inactivation of phosphatidylinositol phosphate 5-kinases" . The Journal of Biological Chemistry . 276 (3): 1865– 1872. doi :10.1074/jbc.M007271200 PMID 11042212 . ^ Mikoshiba, Katsuhiko (1 September 2007). "IP3 receptor/Ca2+ channel: from discovery to new signaling concepts". Journal of Neurochemistry . 102 (5): 1426– 1446. doi :10.1111/j.1471-4159.2007.04825.x . PMID 17697045 . S2CID 4242836 . ^ Christie, William (Bill) W. "Cytidine Diphosphate Diacylglycerol (CDP-DAG), phospholipid biosynthesis - composition and biochemistry" . www.lipidhome.co.uk . Retrieved 19 July 2021 . ^ Liu, Yuan; Wang, Wei; Shui, Guanghou; Huang, Xun (6 March 2014). "CDP-Diacylglycerol Synthetase Coordinates Cell Growth and Fat Storage through Phosphatidylinositol Metabolism and the Insulin Pathway" . PLOS Genetics . 10 (3): e1004172. doi :10.1371/journal.pgen.1004172 PMC 3945474 PMID 24603715 . ^ Bankaitis, Vytas A.; Grabon, Aby (15 November 2011). "Phosphatidylinositol Synthase and Diacylglycerol Platforms Bust a Move" . Developmental Cell . 21 (5): 810– 812. doi :10.1016/j.devcel.2011.10.016 . PMC 3242638 PMID 22075144 . ^ Bout, Iman van den; Divecha, Nullin (1 November 2009). "PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions" J Cell Sci . 122 (21): 3837– 3850. doi :10.1242/jcs.056127 . PMID 19889969 . S2CID 25453017 . Retrieved 3 August 2017 – via jcs.biologists.org.
