| In mammalian cells there are approximately ten phospholipase (PLC) enzymes, including PLC-β, PLC-γ and PLC-δ, which mediate the hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to the second messenger molecules inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Four PLC-β isozymes are regulated by G protein-mediated receptors, while, regulation of the four -δ isozymes is not understood. PLC-γ is the only PLC isoform which has SH2 and SH3 domains, and is activated by several growth factor tyrosine kinase receptors, for example epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). Following the activation of receptor kinases by ligand binding, PLC-γ1 associates with activated receptors, and in turn is phosphorylated on tyrosine residues by these receptor tyrosine kinases. The activated PLC-γ1 thentranslocates to the membrane, and causes the hydrolysis of PIP2. PLC-γ1 activation alsofollows the activation of Rand T cell receptor and involves the activation of cytoplasmictyrosine kinases, which are non-receptor tyrosine kinases.There are two PLC-γ isotypes, PLC-γ1 and PLC-γ2. They have a similar structural organization and high sequence homology, but different patterns of expression and chromosome location. There is evidence that PLC-γ1 may participate in cellular growth and differentiation mediated by receptor tyrosine kinases. Overexpression and amplification of PLC-γ1 has been detected in certain human cancers. However, some observations have indicated that activation of PLC-γ1 seems to be not obligatory for mitogenesis and differentiation under certain conditions. However, these studies do not rule out non-catalytic activities of PLC-γ1, such as the interaction with SH2 and SH3 binding proteins. In order to address the biological function of PLC-γ1 in growth and...
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