Activation of Ras by phorbol esters in cardiac myocytes. Role of guanine nucleotide exchange factors.
The relationship between protein kinase C (PKC) activation and Ras function was investigated in cardiac cells. Ras function was required for ERK activation by phorbol esters in cardiac myocytes, but not in cardiac fibroblasts. Accordingly, treatment with phorbol esters resulted in GTP loading of Ras in cardiac myocytes, but not fibroblasts. Ras activation by phorbol esters was abolished by a PKC specific inhibitor, but was insensitive to tyrosine kinase inhibitors. Ras activation was mediated by stimulation of guanine nucleotide exchange. These results suggest the existence of a novel pathway for Ras activation, specific to cardiac myocytes, with implications for myocardial hypertrophy.
Montessuit
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Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City 84112-5550, USA.
Thorburn
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D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002478:Cells, Cultured; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018631:ras Proteins / Q000235:genetics*
D000470:Alkaloids; D053119:Benzophenanthridines; D020662:Guanine Nucleotide Exchange Factors; D010617:Phenanthridines; D006160:Guanosine Triphosphate; D008148:Lovastatin; C016299:chelerythrine; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate