Serum/glucocorticoid‐inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB
Copyright policy )Serum/glucocorticoid‐inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB
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.
Cell-Free System, Nuclear Proteins, Cyclic AMP response element binding protein, Protein Serine-Threonine Kinases, Dexamethasone, Cell Line, Immediate-Early Proteins, Mice, Serum/glucocorticoid-induced kinase, Animals, Humans, Phosphorylation, Serum-Glucocorticoid Regulated Kinases, Cyclic AMP Response Element-Binding Protein, Protein Binding
Cell-Free System, Nuclear Proteins, Cyclic AMP response element binding protein, Protein Serine-Threonine Kinases, Dexamethasone, Cell Line, Immediate-Early Proteins, Mice, Serum/glucocorticoid-induced kinase, Animals, Humans, Phosphorylation, Serum-Glucocorticoid Regulated Kinases, Cyclic AMP Response Element-Binding Protein, Protein Binding
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