Protein kinase C phosphorylates the inhibitory guanine‐nucleotide‐binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase

Abstract

Human platlet membrane proteins were phosphorylated by exogenous, partially purified Ca2+‐activated phospholipid‐dependent protein kinase (protein kinase C. the phosphorylation of one of the major substrates fro protein kinase C (Mr= 41000) wa specifically suppressed by the β subunit of the inhibitory guaninenucleotide‐binding regulatory component (G1, Ni) of adenylate cyclase. The free α subunit of Gi (Mr= 41000) also served as an excellent substrate for the kinase (<0.5 mol phosphate incorporated per mol of subunit), but the Gi oligomer (α·β·γ) did not. Treatment of cyc‐ S49 lymphoma cells, which are dificient in Gs/Ns(the stimulatory component) but contain functional Gi/Ns, with the phorbol ester, 12‐O‐tetradecanoylophorbol 13‐acetate, a potent activator of protein kinase C, did not alter stimulation of adenylate cyclase catalystic activity by forskolin, whereas the Gi/Ni‐mediated inhibition of the cyclase by the hormone, somatostatin, was impaired in these membranes. The results suggest that the α subunit of the inhibitory guanine‐nucleotide‐binding regulatory component of adenylate cyclase may be a physiological substrate for protein kinase C and that the function of the component in transducing inhibitory hormonal signals to adenylate cyclase is altered by its phosphorylation. Copyright © 1985, Wiley Blackwell. All rights reserved