| Phospholipase C i1 (PLC i1), a phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2)-specific phosphodiesterase plays a critical role in the initiation of receptor-mediated signal transduction through the generation of the two second messengers, inositol 1,4,5-triphosphate and diacylglycerol, from phosphatidylinositol-4,5-bisphosphate. A total of nine mammalian PLC isozymes have been described (PLC i1, PLC i2, PLC i3, PLC i4, PLC i1, PLC i2, PLC i´1, PLC i2 and PLC iµ) with molecular weights ranging from 85 to 255 kDa. The i-type enzymes are unique in that they contain SH2 and SH3 domains. Moreover, the two i-type enzymes, but not the i and i´ isozymes, are subject to activation by a number of protein tyrosine kinases, which associate with SH2 domains and induce their activation by phosphorylation. In contrast, activation of PLC i1, PLC i2 and PLC i3 is mediated by the i subunits of the Gq class of heterotrimeric G proteins and by certain G protein ii subunits. PLC-L (for PLC-deleted in lung carcinoma) plays a role in inositol phospholipid-based intracellular signaling and contributes to the progression of human lung carcinoma. Of the phosphoinositide-specific phospholipase C enzymes, C-beta is regulated by heterotrimeric G protein-coupled receptors, while the closely related C-gamma-1 (PLCG1) and C-gamma-2 (PLCG2) enzymes are controlled by receptor tyrosine kinases. The C-gamma-1 and C-gamma-2 enzymes are composed of phospholipase domains that flank regions of homology to noncatalytic domains of the SRC oncogene product, SH2 and SH3. |
