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Negative regulation of Raf activity by binding of 14-3-3 to the amino terminus of Raf in vivo.
Rommel, C; Radziwill, G; Moelling, K; Hafen, E.
Afiliação
  • Rommel C; Institute of Medical Virology, University of Zuerich, Switzerland.
Mech Dev ; 64(1-2): 95-104, 1997 Jun.
Article em En | MEDLINE | ID: mdl-9232600
ABSTRACT
In the developing eye of Drosophila the protein kinase D-Raf controls the specification of the R7 photoreceptor cells. We show that overexpression of wild-type D-Raf inhibits the formation of R7 cells in a dose-dependent manner. Conversely, overexpression of mutant D-Raf proteins in which the conserved S388 is replaced by A or by D promotes the formation of supernumerary R7 cells, indicating increased D-Raf activity in vivo. S388 in D-Raf corresponds to S259 in c-Raf; shown to be involved in binding of 14-3-3. We show that analogous substitutions of S259 in c-Raf prevent binding of 14-3-3 zeta to the amino terminus of c-Raf and cause a Ras-independent constitutively increased c-Raf kinase activity. Binding of 14-3-3 zeta to the second binding site at the carboxy terminal catalytic domain was unaffected by these mutations. These results suggest that the increased kinase activity of mutant D-Raf is caused by the selective loss of 14-3-3 binding to its amino terminus. Therefore, binding of 14-3-3 to the amino terminus of Raf appears to negatively regulate Raf kinase activity in vivo.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tirosina 3-Mono-Oxigenase / Proteínas / Proteínas Proto-Oncogênicas / Proteínas Serina-Treonina Quinases / Drosophila / Olho Limite: Animals Idioma: En Revista: Mech Dev Assunto da revista: EMBRIOLOGIA Ano de publicação: 1997 Tipo de documento: Article País de afiliação: Suíça
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tirosina 3-Mono-Oxigenase / Proteínas / Proteínas Proto-Oncogênicas / Proteínas Serina-Treonina Quinases / Drosophila / Olho Limite: Animals Idioma: En Revista: Mech Dev Assunto da revista: EMBRIOLOGIA Ano de publicação: 1997 Tipo de documento: Article País de afiliação: Suíça