The study investigates whether the nuclear factor CREB is a regulatory target for the protein kinase Akt/PKB. CREB, which is phosphorylated at Ser-133 by protein kinase A (PKA), is known to stimulate gene expression by recruiting the co-activator CBP. The authors found that overexpressed Akt/PKB in serum-stimulated cells induced Ser-133 phosphorylation of CREB and promoted CBP recruitment. This resulted in increased target gene expression via a phospho-(Ser-133)-dependent mechanism. Akt/PKB activity was specifically required for this effect, as it was suppressed by the PI3-K inhibitor LY 294002. The results suggest that Akt/PKB contributes to cell survival by promoting gene expression through the CREB/CBP pathway.The study investigates whether the nuclear factor CREB is a regulatory target for the protein kinase Akt/PKB. CREB, which is phosphorylated at Ser-133 by protein kinase A (PKA), is known to stimulate gene expression by recruiting the co-activator CBP. The authors found that overexpressed Akt/PKB in serum-stimulated cells induced Ser-133 phosphorylation of CREB and promoted CBP recruitment. This resulted in increased target gene expression via a phospho-(Ser-133)-dependent mechanism. Akt/PKB activity was specifically required for this effect, as it was suppressed by the PI3-K inhibitor LY 294002. The results suggest that Akt/PKB contributes to cell survival by promoting gene expression through the CREB/CBP pathway.