Activation of Ras by phorbol esters in cardiac myocytes - Role of guanine nucleotide exchange factor

The relationship between protein kinase C (PKC) activation and Ras function ,vas investigated in cardiac cells. Ras function was required for ERK activ ation by phorbol esters in cardiac myocytes, but not in cardiac fibroblasts . Accordingly, treatment with phorbol eaters resulted in GTP loading of Res 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 n ucleotide exchange. These results suggest the existence of a novel pathway for Ras activation, specific to cardiac myocytes, with implications for myo cardial hypertrophy. (C) 1999 Federation of European Biochemical Societies.