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Phosphorylation and regulation of Raf by Akt (protein kinase B).

Science (New York, N.Y.) | Nov 26, 1999

Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, or differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.

Pubmed ID: 10576742 RIS Download

Mesh terms: Cell Division | Cell Line | Chromones | Cyclin-Dependent Kinase Inhibitor p21 | Cyclins | Enzyme Activation | Enzyme Inhibitors | Epidermal Growth Factor | Flavonoids | Humans | MAP Kinase Signaling System | Morpholines | Phosphatidylinositol 3-Kinases | Phosphorylation | Phosphoserine | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | Proto-Oncogene Proteins c-raf | Recombinant Fusion Proteins | Signal Transduction | Somatomedins | Tetradecanoylphorbol Acetate | Tumor Cells, Cultured | ras Proteins