Selective inhibition of fibroblast growth factor (FGF)-stimulated mitogenesis by a FGF receptor-1-derived phosphopeptide
| Autor: | D J, Dunican, E J, Williams, F V, Howell, P, Doherty |
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| Rok vydání: | 2001 |
| Předmět: |
Phosphopeptides
MAP Kinase Signaling System Phospholipase C gamma Molecular Sequence Data Proteins Receptor Protein-Tyrosine Kinases 3T3 Cells Salamandridae Receptors Fibroblast Growth Factor Fibroblast Growth Factors Isoenzymes src Homology Domains Mice Type C Phospholipases Animals Amino Acid Sequence Receptor Fibroblast Growth Factor Type 1 Mitogen-Activated Protein Kinases Mitogens Cells Cultured Adaptor Proteins Signal Transducing GRB2 Adaptor Protein |
| Zdroj: | Cell growthdifferentiation : the molecular biology journal of the American Association for Cancer Research. 12(5) |
| ISSN: | 1044-9523 |
| Popis: | The activated fibroblast growth factor receptor (FGFR)-1 is phosphorylated on five tyrosine residues outside the catalytic site. Although one such residue, Tyr730, is flanked by potential binding sites for phosphotyrosine-interacting molecules, a physiological role for this region is still controversial. We report that a cell-permeant phosphopeptide mimic of this site, FGFR730(p)Y, inhibits FGF-mediated mitogenesis in cells with no effect on responses stimulated by other growth factors. A similar phosphopeptide corresponding to the phospholipase Cgamma binding site on the receptor had no effect on the mitogenic response. The FGFR730(p)Y peptide did not inhibit phosphorylation of p90/FRS2 or Erk, suggesting that it does not act by inhibiting the Erk-kinase cascade. However, the FGFR730(p)Y peptide bound Shc in a manner requiring both phosphorylated tyrosine and a putative PTB domain binding determinant. These data suggest that the peptide might inhibit mitogenesis by competing with the corresponding site on the FGFR for the ability to bind SHC. |
| Databáze: | OpenAIRE |
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