Regulation of Akt/PKB Activation by Tyrosine Phosphorylation
| Autor: | James B. McCarthy, Kanoka Sato, Riyan Chen, Oekyung Kim, Kathryn M. Eisenmann, Hegang Chen, Jiangbo Yang, Yun Qiu |
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| Rok vydání: | 2001 |
| Předmět: |
Molecular Sequence Data
Protein tyrosine phosphatase Protein Serine-Threonine Kinases SRC Family Tyrosine Kinase Biochemistry Receptor tyrosine kinase Cell Line Oncogene Protein pp60(v-src) Mice chemistry.chemical_compound Proto-Oncogene Proteins Animals Humans Amino Acid Sequence Phosphorylation Molecular Biology Protein kinase B biology Akt/PKB signaling pathway Tyrosine phosphorylation Cell Biology Cell biology Enzyme Activation chemistry Cancer research biology.protein Tyrosine Proto-Oncogene Proteins c-akt Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Biological Chemistry. 276:31858-31862 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.c100271200 |
| Popis: | Activation of Akt/PKB by growth factors requires multiple phosphorylation events. Phosphorylation of Thr(308) and Ser(473) of Akt by its upstream kinase(s) or autophosphorylation is critical for optimal activation of its kinase activity. Here, we present evidence that tyrosine phosphorylation is required for Akt activation. Epidermal growth factor treatment induces tyrosine phosphorylation of Akt in COS1 and PC3M cells, which is abrogated by PP2, a selective inhibitor for Src family tyrosine kinases. Elevated Akt activity is observed in v-Src transformed NIH3T3 cells, which is accompanied with increased tyrosine phosphorylation of Akt. Akt activity induced by growth factors is significantly reduced in SYF cells lacking Src, Yes, and Fyn, which can be restored by introducing c-Src, but not the kinase-inactive Src, back to these cells. Furthermore, we have identified two tyrosine residues near the activation loop of Akt that are important for its activation. Substitution of these residues with phenylalanine abolishes Akt kinase activity stimulated by growth factors. These two YF mutants fail to block Forkhead transcription factor activity in 293 cells and are unable to prevent apoptosis induced by matrix detachment. Our data suggest that, in addition to phosphorylation of Thr(308) and Ser(473), tyrosine phosphorylation of Akt may be essential for its biological function. |
| Databáze: | OpenAIRE |
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