title: Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.
abstract: To identify proteins that may participate in the activation of the protein kinase Raf, proteins that interact with Raf were selected in a two-hybrid screen. Two members of the 14-3-3 protein family were isolated that interacted with both the amino terminal regulatory regions of Raf and the kinase domain of Raf, but did not compete with the guanine nucleotide-binding protein Ras for binding to Raf. 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. In yeast cells expressing Raf and MEK, mammalian 14-3-3 beta or 14-3-3 zeta activated Raf to a similar extent as did expression of Ras. Therefore, 14-3-3 proteins may participate in or be required for the regulation of Raf function. These findings suggest a role for 14-3-3 proteins in Raf-mediated signal transduction.
authors.affiliation: Onyx Pharmaceuticals, Richmond, CA 94806-5206.
authors.forename: E
authors.initials: E
authors.lastname: Freed
authors.forename: M
authors.initials: M
authors.lastname: Symons
authors.forename: S G
authors.initials: SG
authors.lastname: Macdonald
authors.forename: F
authors.initials: F
authors.lastname: McCormick
authors.forename: R
authors.initials: R
authors.lastname: Ruggieri
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase; D016335:Zinc Fingers
chemical_list: D048948:14-3-3 Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins