Abstract
Raf-1 is a serine/threonine kinase that acts downstream of Ras in mitogenic signal transduction pathways, but the mechanism by which Ras transmits signals to Raf-1 is not known. We have examined the interaction between Raf-1 and human H-ras in three different systems that utilize H-ras-induced phenotypes in Saccharomyces cerevisiae. In each system, the effects of H-ras depend on guanosine triphosphate and appear to be mediated through the H-ras effector binding region. H-ras effector function was blocked in each case by expression of the N-terminal regulatory domain of Raf-1. These inhibitory effects did not require the Raf-1 kinase domain. Raf-1 also blocked Rap1A effector function in S. cerevisiae. Raf-1, therefore, appears to interact with H-Ras and Rap1A in these in vivo systems with properties that suggest it is an immediate downstream effector.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Cycle Proteins*
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Fungal Proteins / metabolism
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GTP-Binding Proteins / metabolism*
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Genes, ras
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Guanine Nucleotide Exchange Factors*
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Guanosine Triphosphate / metabolism
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Humans
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Phenotype
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Protein Serine-Threonine 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) / genetics
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Proto-Oncogene Proteins p21(ras) / metabolism*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Signal Transduction
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Temperature
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Transcription Factors / metabolism
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rap GTP-Binding Proteins
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ras-GRF1*
Substances
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CDC24 protein, S cerevisiae
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CDC25 protein, S cerevisiae
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Cell Cycle Proteins
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Fungal Proteins
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Guanine Nucleotide Exchange Factors
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Proto-Oncogene Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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ras-GRF1
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Guanosine Triphosphate
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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GTP-Binding Proteins
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)
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rap GTP-Binding Proteins