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FEBS Lett. 2005 Feb 28;579(6):1534-8.

Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB.

Author information

1
Children's Hospital of Philadelphia, Joseph Stokes Jr. Research Institute, ARC 814, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
2
Children's Hosp of Philadelphia, PA

Abstract

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 1 (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.

PMID:
15733869
DOI:
10.1016/j.febslet.2005.01.040
[Indexed for MEDLINE]
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