Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases
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Cell Line
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Gene Expression Regulation
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Genes, Regulator*
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Genes, ras*
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Nerve Growth Factors / pharmacology
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PC12 Cells / drug effects
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Phorbol Esters / pharmacology
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Phosphorylation / drug effects
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Protein Kinase C / metabolism*
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Protein Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-raf
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Proto-Oncogene Proteins p21(ras)*
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / metabolism*
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Receptors, Nerve Growth Factor
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Ribosomal Protein S6 Kinases
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Signal Transduction
Substances
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Nerve Growth Factors
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Phorbol Esters
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, Nerve Growth Factor
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Protein Kinases
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Proto-Oncogene Proteins c-raf
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Ribosomal Protein S6 Kinases
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinases
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Proto-Oncogene Proteins p21(ras)