Ras activity is required for phenylephrine-induced activation of mitogen-activated protein kinase in cardiac muscle cells.
The mitogen-activated protein (MAP) kinases are a family of kinases whose activity is implicated in a number of growth and differentiation responses. Recently, we and others have shown that these kinases are activated by agonists which induce cardiac muscle cell hypertrophy. Inhibition of MAP kinase activation prevents some of the phenotypes associated with phenylephrine-induced cardiac cell hypertrophy, indicating that this activation is of functional significance. In this communication, we show that active Ras can induce MAP kinase activation in cardiac muscle cells. In addition, phenylephrine-induced activation of the MAP kinases requires Ras activity since a dominant negative Ras mutant (Ala15Ras) and a Ras-blocking, Raf mutant (C4B Raf) prevent activation of the MAP kinase Erk2 by phenylephrine. These data indicate that phenylephrine signaling to the MAP kinases is mediated through Ras.
Thorburn
A
A
Dept. of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City 84112.
D000818:Animals; D000831:Animals, Newborn; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006352:Heart Ventricles; D019950:Mitogen-Activated Protein Kinase 1; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000201:enzymology*; D010656:Phenylephrine / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D014162:Transfection; D018631:ras Proteins / Q000096:biosynthesis / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D010656:Phenylephrine; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D018631:ras Proteins