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