Du K, Montminy M
Joslin Diabetes Center, Research Division, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Biol Chem. 1998 Dec 4;273(49):32377-9. doi: 10.1074/jbc.273.49.32377.
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.
核因子CREB在其丝氨酸133位点经蛋白激酶A介导的磷酸化后，可刺激细胞基因的表达。反过来，丝氨酸133位点的磷酸化通过促进共激活因子CBP的募集来激活靶基因的表达。最近的研究表明，某些细胞类型的存活需要CREB及其旁系同源物CREM，这促使我们研究CREB是否是生长因子依赖性丝氨酸/苏氨酸激酶Akt/PKB激活的核靶点。当在血清刺激的细胞中过表达时，Akt/PKB能有效诱导CREB的丝氨酸133位点磷酸化，并促进CBP的募集。相应地，Akt/PKB通过CREB以磷酸化（丝氨酸133）依赖性方式刺激靶基因的表达。Akt/PKB仅在对血清刺激作出反应时诱导CREB活性，并且这种效应被磷脂酰肌醇3激酶抑制剂LY 294002所抑制。我们的结果支持这样一种观点，即Akt/PKB至少部分地通过CREB/CBP核转导途径刺激细胞基因的表达来促进细胞存活。
