ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.
p21c-ras plays a critical role in mediating tyrosine kinase-stimulated cell growth and differentiation. However, the pathways through which p21c-ras propagates these signals remain unknown. We report that in PC12 cells, expression of a dominant inhibitory mutant of ras, c-Ha-ras(Asn-17), antagonizes growth factor- and phorbol ester-induced activation of the erk-encoded family of MAP kinases, the 85-92 kd RSKs, and the kinase(s) responsible for hyperphosphorylation of the proto-oncogene product Raf-1. In addition, we find that expression of the activated ras oncogene is sufficient to stimulate these events. These data indicate that ras mediates nerve growth factor receptor and protein kinase C modulation of MAP kinases, RSKs, and Raf-1.
Wood
K W
KW
Program in Cell and Developmental Biology, Harvard University, Boston, Massachusetts.
Sarnecki
C
C
Roberts
T M
TM
Blenis
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D011905:Genes, ras; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras); D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction
D009414:Nerve Growth Factors; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D011494:Protein Kinases; D019908:Proto-Oncogene Proteins c-raf; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)