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

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Citation

David S, Kalb RG

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

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

PubMed ID
15733869 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cyclic AMP-responsive element-binding protein 1P16220Details
Serine/threonine-protein kinase Sgk1O00141Details