Differential regulation of 46 and 54 kDa jun N-terminal kinases and p38 mitogen-activated protein kinase by human alpha(1A)-adrenoceptors expressed in Rat-1 cells.
We have investigated the alpha(1A)-adrenoceptor-mediated activation of 46 and 54 kDa isoforms of c-jun N-terminal kinase (JNK) and of p38 mitogen-activated protein kinase. The alpha(1)-adrenoceptor agonist phenylephrine activated all three kinases but with different time courses and maximal effects. Activation of all three kinases was insensitive to the phosphatidylinositol-3-kinase inhibitor wortmannin but was enhanced by the protein kinase C inhibitor bisindolylmaleimide I; a protein kinase C-activating phorbol ester inhibited JNK but not p38 activation. Activation of 54 kDa JNK, but not of the other two kinases, was inhibited by pertussis toxin and the phospholipase C inhibitor U 73,122. We conclude that alpha(1)-adrenoceptor stimulation activates 46 kDa JNK, 54 kDa JNK and p38 but uses at least partly different pathways to do so.
Alexandrov
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A
Departments of Medicine and Urology, University of Essen, Essen, Germany.
Keffel
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Goepel
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Michel
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MC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
C547713:ADRA1A protein, human; C547715:Adra1a protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000730:Androstadienes; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D008301:Maleimides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010656:Phenylephrine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin; D000077191:Wortmannin