G-protein beta gamma subunits antagonize protein kinase C-dependent phosphorylation and inhibition of phospholipase C-beta(1)

Protein kinase C (PKC) isoforms phosphorylated phospholipase C-beta(1) (PLC-beta(1)) in vitro as follows: PKC alpha much greater than PKC epsilon; not PKC zeta, PLC-beta(3) was not phosphorylated by PKC alpha. G-protein beta gamma subunits inhibited the PKC alpha phosphorylation of PLC-beta 1 in a concentration-dependent manner. Half-maximal inhibition occurred with 500 beta gamma. G-protein beta gamma subunits also antagonized the PKC alpha-mediated inhibition of PLC-beta(1) enzymic activity. PKC alpha, in turn, inhibitied the stimulation of PLC-beta(1) activity by beta gamma. There was little effect of PKC alpha on the stimulation of PLC-beta(1) by alpha(q/11)-guanosine 5'[gamma-thio]tiphosphate (GTP[S]). These findings demonstrate that G protein beta gamma subunits antagonize PKC alpha regulation of PLC-beta(1). Thus beta gamma subunits might have a role in modulating the negative feedback regulation of this signaling system by PKC.