REGULATION OF PHOSPHOINOSITIDE PHOSPHOLIPASES BY HORMONES, NEUROTRANSMITTERS, AND OTHER AGONISTS LINKED TO G-PROTEINS

The actions of many hormones, neurotransmitters, and growth factors ar e mediated by the hydrolysis of phosphatidylinositol 4,5-bisphosphate catalyzed by specific isozymes of phospholipase C. This hydrolysis rel eases inositol 1,4,5- trisphosphate, which mobilizes Ca2+ ions from co mponents fo the endoplasmic reticulum, and 1,2-diacylglycerol, which a ctivates isozymes of protein kinase C. The hormones and neurotransmitt ers activate beta-isozymes of phospholipase C through receptors that h ave seven transmembrane segments and couple to G proteins of the G(q) and G(i/o) families. Activation of phospholipase C by the G(q) family involves their alpha-subunits, whereas activation by the G(i/o) family involves their beta gamma-subunits. The growth factors activate gamma -isozymes of phospholipase C through receptors that become autophospho rylated due to their stimulated tyrosine kinase activity and provide b inding sites for the Src homology domains of the isozymes. The molecul ar mechanisms by which agonists activate phopholipase isozymes are des cribed in detail.