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

被引:830
作者
Du, KY [1 ]
Montminy, M [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA
关键词
D O I
10.1074/jbc.273.49.32377
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 CREE 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.
引用
收藏
页码:32377 / 32379
页数:3
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