ACTIVATION OF THE BETA-1 ISOZYME OF PHOSPHOLIPASE-C BY ALPHA-SUBUNITS OF THE GQ CLASS OF G-PROTEINS

MANY hormones, neurotransmitters and growth factors, on binding to G protein-coupled receptors or receptors possessing tyrosine kinase activity, increase intracellular levels of the second messengers inositol 1,4,5-trisphophate and 1,2-diacylglycerol. This is due to activation of phosphoinositide-specific phospholipase(s) C (PLC), the isozymes of which are classified into groups, alpha, beta, gamma and delta (refs 1, 2). The beta, gamma and delta-groups themselves contain PLC isozymes which have both common and unique structural domains 3. Only the gamma-1 isozyme has been implicated in a signal transduction mechanism 4. This involves association with, and tyrosine phosphorylation by, the ligand-bound epidermal growth factor and platelet-derived growth factor receptors 5-7, probably by means of the PLC-gamma-1-specific src homology (SH2) domain 8. Because EGF receptor-mediated tyrosine phosphorylation of PLC-gamma-1 stimulates catalytic activity in vitro 9 and G proteins have been implicated in the activation of PLC 10, we investigated which PLC isozymes are subject to G protein regulation. We have purified 11 an activated G protein alpha-subunit that stimulates partially purified phospholipase C and now report that this G protein specifically activates the beta-1 isozyme, but not the gamma-1 and delta-1 isozymes of phospholipase C. We also show that this protein is related to the G(q) class of G protein alpha-subunits 12.