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

Science. 1999 Nov 26;286(5445):1741-4. doi: 10.1126/science.286.5445.1741.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division*
  • Cell Line
  • Chromones / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Flavonoids / pharmacology
  • Humans
  • MAP Kinase Signaling System*
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Somatomedins / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • ras Proteins / metabolism

Substances

  • CDKN1A protein, human
  • Chromones
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Flavonoids
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Somatomedins
  • Phosphoserine
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Epidermal Growth Factor
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • ras Proteins
  • Tetradecanoylphorbol Acetate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one