SUBUNITS-BETA-GAMMA OF HETEROTRIMERIC G-PROTEIN ACTIVATE BETA-2 ISOFORM OF PHOSPHOLIPASE-C

THE activation of heterotrimeric G proteins results in the exchange of GDP bound to the alpha-subunit for GTP and the subsequent dissociation of a complex of the beta- and gamma-subunits (G(betagamma)). The alpha-subunits of different G proteins interact with a variety of effectors1-7, but less is known about the function of the free G(betagamma) complex. G(betagamma) has been implicated in the activation of a cardiac potassium channel8, a retinal phospholipase A2 (ref. 9) and a specific receptor kinase10, and in vitro reconstitution experiments indicate that the G(betagamma) complex can act with G(alpha) subunit to modulate the activity of different isoforms of adenylyl cyclase11. Of two phospholipase activities that can be separated in extracts of HL-60 cells, purified G(betagamma) is found to activate one of them12. Here we report that in co-transfection assays G(betagamma) subunits specifically activate the beta2 and not the beta1 isoform of phospholipase, which acts on phosphatidylinositol. We use transfection assays to show also that receptor-mediated release of G(betagamma) from G proteins that are sensitive to pertussis toxin can result in activation of the phospholipase. This effect may be the basis of the pertussis-toxin-sensitive phospholipase C activation seen in some cell systems (reviewed in refs 13 and 14).