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

T. Katada, A. G. Gilman, Y. Watanabe, S. Bauer, K. H. Jakobs

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Abstract

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 (M(r)=41000) was specifically suppressed by the β subunit of the inhibitory guanine-nucleotide-binding regulatory component (G(i), N(i)) of adenylate cyclase. The free α subunit of G(i) (M(r)=41000) also served as an excellent substrate for the kinase (>0.5 mol phosphate incorporated per mol of subunit), but the G(i) oligomer (α.β.γ) did not. Treatment of cyc- S49 lymphoma cells, which are deficient in G(s)/N(s) (the stimulatory component) but contain functional G(i)/N(i), 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 G(i)/N(i)-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.

Original languageEnglish (US)
Pages (from-to)431-437
Number of pages7
JournalEuropean Journal of Biochemistry
Volume151
Issue number2
DOIs
StatePublished - 1985

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Guanine Nucleotides
Adenylyl Cyclases
Protein Kinase C
Phosphorylation
Substrates
Phorbol Esters
Colforsin
Platelets
Somatostatin
Oligomers
Protein Kinases
Tetradecanoylphorbol Acetate
Catalyst activity
Phospholipids
Membrane Proteins
Acetates
Phosphotransferases
Phosphates
Hormones
Lymphoma

ASJC Scopus subject areas

  • Biochemistry

Cite this

Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppressed its function in hormonal inhibition of adenylate cyclase. / Katada, T.; Gilman, A. G.; Watanabe, Y.; Bauer, S.; Jakobs, K. H.

In: European Journal of Biochemistry, Vol. 151, No. 2, 1985, p. 431-437.

Research output: Contribution to journalArticle

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