共 31 条
Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB
被引:38
作者:
David, S
[1
]
Kalb, RG
[1
]
机构:
[1] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA
来源:
FEBS LETTERS
|
2005年
/
579卷
/
06期
关键词:
serum/glucocorticoid-induced kinase;
cyclic AMP response element binding protein;
dexamethasone;
phosphorylation;
D O I:
10.1016/j.febslet.2005.01.040
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:
To maintain homeostasis, cells often respond to stressful extra-cellular stimuli by new gene expression. Serum/glucocorticoid-induced kinase (SGK) is an immediate early gene whose expression is induced by a variety of extra-cellular stimuli. Here, we examine the possibility that SGK can directly phosphorylate the transcription factor cyclic AMP response element binding protein (CREB). In a cell-free context, SGK physically associates with CREB and SGK phosphorylates it on serine 133. Phospho-serine 133 is essential for stimulating the transcriptional activity of CREB. Further, we show that in a variety of cellular contexts, SGK phosphorylates CREB. Activation of receptor tyrosine kinase pathways or the phosphoinositide-dependent kinase I (PDK1) lead to SGK-dependent CREB phosphorylation. Hormonal stimulation of epithelial cells leads to the induction of endogenous SGK and CREB phosphorylation. A dominant-negative form of SGK blocks dexamethasone-induced CREB phosphorylation. Our studies indicate that stimulation of SGK can lead to CREB phosphorylation, suggesting that CREB-dependent gene transcription is an important link between stressful extra-cellular signals and cellular responses. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1534 / 1538
页数:5
相关论文