Subunits βγ of heterotrimeric G protein activate β2 isoform of phospholipase C

THE activation of heterotrimeric G proteins results in the exchange of GDP bound to the α-subunit for GTP and the subsequent dissociation of a complex of the β- and γ-subunits (Gβγ). The α -subunits of different G proteins interact with a variety of effectors 1–7 , but less is known about the function of the free Gβγ complex. Gβγ has been implicated in the activation of a cardiac potassium channel 8 , a retinal phospholipase A 2 (ref. 9) and a specific receptor kinase 10 , and in vitro reconstitution experiments indicate that the G βγ complex can act with G α subunit to modulate the activity of different isoforms of adenylyl cyclase 11 . Of two phospholipase activities that can be separated in extracts of HL-60 cells, purified G βγ is found to activate one of them 12 . Here we report that in co-transfection assays G βγ subunits specifically activate the β2 and not the β1 isoform of phospholipase, which acts on phosphatidylinositol. We use transfection assays to show also that receptor-mediated release of G βγ 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).