G-protein βγ subunits antagonize protein kinase C-dependent phosphorylation and inhibition of phospholipase C-β₁

Protein kinase C (PKC) isoforms phosphorylated phospholipase C-β₁ (PLC-β₁) in vitro as follows: PKCα ≫ PKCϵ; not PKCζ. PLC-β₃ was not phosphorylated by PKCα. G-protein βγ subunits inhibited the PKCα phosphorylation of PLC-β₁ in a concentration-dependent manner. Half-maximal inhibition occurred with 500 nM βγ. G-protein βγ subunits also antagonized the PKCα-mediated inhibition of PLC-β₁ enzymic activity. PKCα, in turn, inhibited the stimulation of PLC-β₁ activity by βγ. There was little effect of PKCα on the stimulation of PLC-β₁ by α_q/11–guanosine 5′[γ-thio]triphosphate (GTP[S]). These findings demonstrate that G protein βγ subunits antagonize PKCα regulation of PLC-β₁. Thus βγ subunits might have a role in modulating the negative feedback regulation of this signalling system by PKC.