CREB is a regulatory target for the protein kinase Akt/PKB
CREB is a regulatory target for the protein kinase Akt/PKB
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DOI：
10.1074/jbc.273.49.32377
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发表时间：
1998-12-04
影响因子：
4.8
通讯作者：
Montminy, M
中科院分区：
文献类型：
--
作者：
Du, KY;Montminy, M
核因子CREB在其蛋白激酶A介导的Ser-133磷酸化后刺激细胞基因的表达。Ser-133磷酸化反过来通过促进共激活因子CBP的募集来激活靶基因表达。最近的研究表明CREE及其旁的CREM是某些细胞类型存活所必需的，这促使我们检查CREB是否是通过生长因子依赖性Ser/Thr激酶Akt/PKB激活的核靶点。Akt/PKB在血清刺激的细胞中过表达时，可诱导CREB的Ser-133磷酸化，促进CBP的募集，相应地，Akt/PKB以磷酸化（Ser-133）依赖的方式通过CREB促进靶基因的表达。Akt/PKB诱导CREB活性只在血清刺激，这种效果被抑制磷脂酰肌醇3-激酶抑制剂LY 294002。我们的研究结果支持Akt/PKB促进细胞存活的观点，至少部分是通过CREB/CBP核转导途径刺激细胞基因的表达。
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.