CREB is a regulatory target for the protein kinase Akt/PKB.

The nuclear factor CREB stimulates the expression of cellular genes following its protein kinase A-mediated phosphorylation at Ser-133. Ser-133 phosphorylation, in turn, activates target gene expression by promoting recruitment of the co-activator CBP. Recent studies showing that CREB and its paralog CREM are required for survival of certain cell types ...
prompted us to examine whether CREB is a nuclear target for activation via the growth factor-dependent Ser/Thr kinase Akt/PKB. When overexpressed in serum-stimulated cells, Akt/PKB potently induced Ser-133 phosphorylation of CREB and promoted recruitment of CBP. Correspondingly, Akt/PKB stimulated target gene expression via CREB in a phospho(Ser-133)-dependent manner. Akt/PKB induced CREB activity only in response to serum stimulation, and this effect was suppressed by the phosphatidylinositol 3-kinase inhibitor LY 294002. Our results support the notion that Akt/PKB promotes cell survival, at least in part, by stimulating the expression of cellular genes via the CREB/CBP nuclear transduction pathway.
Mesh Terms:
Cell Line, Chloramphenicol O-Acetyltransferase, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, Enzyme Induction, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors
J. Biol. Chem.
Date: Dec. 04, 1998
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