Protein kinase C alters the responsiveness of adenylyl cyclases to G protein alpha and beta gamma subunits

The ability of protein kinase C (PKC) to regulate the responsiveness of adenylyl cyclase to different activators was assessed, Membranes prepared from Sf9 cells infected with recombinant baculoviruses encoding either type II or IV adenylyl cyclase were incubated with recombinant PKC alpha (purified from Sf9 cells), and the effects on adenylyl cyclase activity were measured after reconstitution with G(s alpha), G beta gamma, or forskolin, PKC alpha treatment of type II adenylyl cyclase leads to increases in basal, forskolin-stimulated, and beta gamma-stimulated activities and greater sensitivity to stimulation by G(s alpha). Paradoxically, most of the beta gamma potentiation of G(s alpha)-stimulated activity is eliminated by pretreatment with PKC alpha, By contrast, treatment of type IV adenylyl cyclase with PKC alpha has little effect on the basal, forskolin-stimulated, or beta gamma-stimulated activities but markedly reduces the G(s alpha)-stimulated and beta gamma-potentiated activity of this isoform. These studies demonstrate that protein kinases can alter both the activity of adenylyl cyclase isoforms and their responsiveness to G protein regulation, thereby altering the ability of adenylyl cyclases to integrate signals derived from multiple hormonal inputs.