title: [The mechanism of phospholipase Cγ1 activation].
abstract: Phospholipase C is an enzyme which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) 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 Ca(2+) 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. PLCγ 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. PLCγ1 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)P(2)). 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.
authors.affiliation: Laboratorium Białek Sygnałowych Instytutu Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Janusz
authors.initials: J
authors.lastname: Matuszyk
mesh_terms: D001921:Brain / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008168:Lung / Q000201:enzymology; D010712:Phosphatidic Acids / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland / Q000201:enzymology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D010712:Phosphatidic Acids; D016875:tau Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051966:Phospholipase C gamma