Phosphoinositide-specific phospholipase C (PLC) plays a significant role in transmembrane signaling. In response to extracellular stimuli, such as hormones, growth factors and neurotransmitters, PLC hydrolyzes phosphatidylinositol 4,5-biphosphate (PIP2) to generate two secondary messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) (1). At least four families of PLCs have been identified: PLCbeta, PLCgamma, PLCdelta and PLCepsilon. The PLCbeta subfamily includes four members, PLCbeta1-4. All four members of the subfamily are activated by alpha-or betagamma-subunits of the heterotrimeric G-proteins (2,3). Phosphorylation is one of the key mechanisms that regulates the activity of PLC. Phosphorylation of serine 1105 by PKA or PKC inhibits PLCbeta3 activity (4,5). Serine 537 of PLCbeta3 is phosphorylated by CaMKII and this phosphorylation may contribute to the basal activity of PLCbeta3. PLCgamma is activated by both receptor and nonreceptor tyrosine kinases (6). PLCgamma forms a complex with EGF and PDGF receptors, which leads to the phosphorylation of PLCgamma1 on tyrosine residues 771, 783 and 1245 (7). Phosphorylation by Syk at tyrosine 783 activates the enzymatic activity of PLCgamma1 (8). PLCgamma2 is engaged in antigen-dependent signaling in B cell and collagen-dependent signaling in platelets. Phosphorylation by Btk or Lck at tyrosines 753, 759, 1197 and 1217 is correlated with PLCgamma2 activity (9,10).
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