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The mechanism of phospholipase Cγ1 activation

Author(s): Paweł Krawczyk | Janusz Matuszyk

Journal: Postępy Higieny i Medycyny Doświadczalnej
ISSN 0032-5449

Volume: 65;
Issue: 846636;
Start page: 470;
Date: 2011;
Original page

Keywords: fosfolipaza Cγ1 | mechanizm aktywacji fosfolipazy Cγ1 | metabolizm fosfatydyloinozytolu | receptorowe kinazy tyrozynowe | phospholipase Cγ1 | activation mechanism of phospholipase Cγ1 | phosphoinositide metabolism | receptor tyrosine kinase

Phospholipase C is an enzyme which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) into second messengers inositol-1,4,5-triphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG). These messengers then promote the activation of protein kinase C and release of Ca2 from intracellular stores, initiating numerous cellular events including proliferation, differentiation, signal transduction, endocytosis, cytoskeletal reorganization or activation of ion channels. There have been identified 14 isozymes of PLC among which PLCγ1 and PLCγ2 are of particular interest. PLC contains catalytic region XY and a few regulatory domains: PH, EF and C2. The most unique features of these two enzymes are the Src homology domains (SH2, SH3) and split PH domain within the catalytic barrel. PLC1 and PLCγ2 have an identical domain structure, but they differ in their function and occurrence. Phospholipase Cγ1 is expressed ubiquitously, especially in the brain, thymus and lungs.PLCγ1 can be activated by receptor tyrosine kinases (i.e.: PDGFR, EGFR, FGFR, Trk), as well as non-receptor protein kinases (Src, Syk, Tec) or phosphatidic acid, tau protein and its analogue.The molecular mechanism of PLCγ1 activation includes membrane recruitment, phosphorylation, rearrangements and activation in the presence of growth factors.In reference to PLCγ1 regulation, a number of positive and negative modulators have been considered. The most important positive modulator is phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P2). Protein kinase A and C, tyrosine phosphatases (SHP-1, PTP-1B) and Cbl, Grb2, Jak2/PTP-1B complex proteins have been described as negative regulators of PLCγ1 activation.

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