Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase.
Human platelet 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 for protein kinase C (Mr = 41 000) was specifically suppressed by the beta subunit of the inhibitory guanine-nucleotide-binding regulatory component (Gi, Ni) of adenylate cyclase. The free alpha subunit of Gi (Mr = 41 000) also served as an excellent substrate for the kinase (greater than 0.5 mol phosphate incorporated per mol of subunit), but the Gi oligomer (alpha X beta X gamma) did not. Treatment of cyc- S49 lymphoma cells, which are deficient in Gs/Ns (the stimulatory component) but contain functional Gi/Ni, with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate, a potent activator of protein kinase C, did not alter stimulation of adenylate cyclase catalytic 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 alpha 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.
Katada
T
T
Gilman
A G
AG
Watanabe
Y
Y
Bauer
S
S
Jakobs
K H
KH
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D008565:Membrane Proteins; D011494:Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases