Evidence for selective regulation of the phosphorylation of myocyte proteins by isoproterenol and prostaglandin E1.
Both isoproterenol and prostaglandin E1 increased the activation state of cyclic AMP-dependent protein kinase in cultured myocytes; however, only isoproterenol enhanced phosphorylase activity and contractile state. Following the incubation of intact myocytes with 32PO3-(4), 32 phosphoproteins were resolved from total cellular proteins by electrophoresis in sodium dodecyl sulfate polyacrylamide gels followed by autoradiography. Isoproterenol stimulated 32PO3-(4) incorporation into 16 proteins, including 2 phosphoproteins not observed under control conditions. By contrast, prostaglandin E1 neither caused a measurable change in the protein phosphorylation pattern nor interfered with isoproterenol's capacity to do so. Isoproterenol stimulated myocyte protein phosphorylation in either the presence or absence of extracellular Ca2+. The results suggest that the regulation of protein phosphorylation following adenylate cyclase stimulation is: (1) an agonist-specific process and not due solely to a random accumulation of intracellular cycle AMP and activation of protein kinase; (2) the Ca2+ mobilization component of beta-receptor activation does not account for the paradoxical effects of isoproterenol and prostaglandin E1; (3) activation of cyclic AMP-dependent protein kinase does not always result in an enhancement of protein phosphorylation.
D000527:Alprostadil; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D011458:Prostaglandins E; D011506:Proteins; D000242:Cyclic AMP; D006005:Phosphorylases; D011494:Protein Kinases; D000527:Alprostadil; D007545:Isoproterenol