Pertussis toxin-sensitive and insensitive guanine nucleotide binding proteins (G-proteins) are not phosphorylated by cyclic GMP-dependent protein kinase.
Cyclic GMP mediates vascular smooth muscle relaxation to a variety of drugs and naturally-occurring substances. The reduction of intracellular Ca2+ levels is believed to underlie this action, but the mechanism of this effect is unknown. In order to test the hypothesis that inhibition of guanine nucleotide-binding protein function is involved in the actions of cGMP, the effects of cGMP-dependent protein kinase on the phosphorylation of both pertussis toxin-sensitive (Gi/Go) and insensitive (Gz) G-proteins were examined in vitro. None of these proteins were effective substrates for either cGMP- or cAMP-dependent protein kinases, despite the fact that assay conditions were designed to detect poorly phosphorylated substrate proteins. In line with these observations, atriopeptin II did not inhibit angiotensin II-treated inositol phosphate formation in cultured vascular smooth muscle cells. These results suggest that phosphorylation by cGMP-dependent protein kinase of these G-proteins is not the major mechanism by which cGMP reduces intracellular Ca2+ levels in vascular smooth muscle.
Lincoln
T M
TM
Department of Pharmacology, University of South Alabama College of Medicine, Mobile 36688.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000187:drug effects*; D007295:Inositol Phosphates / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments; D037342:Pertussis Toxin; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000187:drug effects; D013379:Substrate Specificity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007295:Inositol Phosphates; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D009320:Atrial Natriuretic Factor; C062524:atrial natriuretic factor prohormone (103-125); D037342:Pertussis Toxin; D011494:Protein Kinases; D019204:GTP-Binding Proteins