Signal transduction pathways involving the Raf proto-oncogene.
The raf genes encode for a family of cytoplasmic proteins (A-raf, B-raf and c-raf-1) with associated serine/threonine kinase activities. Raf-1 is an important mediator of signals involving cell growth, transformation and differentiation. It is activated in response to a wide variety of extracellular stimuli such as insulin, nerve growth factor (NGF), platelet derived-growth factor (PDGF), and in response to expression of oncogenes, v-src and v-ras, in a cell-specific manner. Recently, the first physiological substrate for Raf-1 protein kinase was identified. Raf-1 was found to phosphorylate and activate Mitogen-Activated Protein Kinase Kinase (MEK), an activator of MAP kinase, thus linking the Raf-1 signaling pathway with that of MAP kinase. Cell specific differences in signalling pathways involving Raf-1 and MAP kinase have also been discovered. Accumulating evidence indicates that membrane tyrosine kinases, ras, Raf-1, MEK and MAP kinase are interconnected via a complex network rather than via a linear pathway involving multiple substrates and feedback loops.
Williams
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Roberts
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TM
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D015398:Signal Transduction; D013379:Substrate Specificity
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins