Regulation of phospholipase C isozymes: activation of phospholipase C-gamma in the absence of tyrosine-phosphorylation

Activation of PLC-gamma isozymes in response to various agonists involves t yrosine phosphorylation of the effector enzymes. Recent evidence indicates that PLC-gamma isozymes are additionally activated by phosphatidic acid, ph osphatidylinositol 3,4,5-trisphosphate and arachidonic acid in the absence of PLC-gamma tyrosine phosphorylation. These lipid-derived messengers are t he immediate products of phospholipase D, phosphatidylinositol 3-kinase, an d phospholipase A(2), enzymes which are often stimulated along with PLC-gam ma in response to an agonist. Furthermore, phosphatidylinositol 4,5-bisphos phate acts as a substrate for both PLC-gamma and phosphatidylinositol 3-kin ase and as an activator for phospholipase D and phospholipase A(2). These r esults reveal an elaborate mechanism of cross-talk and mutual regulation be tween four effector enzymes that participate in receptor signaling by actin g on phospholipids. (C) 1999 Elsevier Science Ireland Ltd. All rights reser ved.