Document Detail

Serum- and glucocorticoid-inducible kinase (SGK) is a target of the MAPK/ERK signaling pathway that mediates memory formation in rats.
MedLine Citation:
PMID:  16553792     Owner:  NLM     Status:  MEDLINE    
We have previously demonstrated that serum- and glucocorticoid-inducible kinase (SGK) plays a causal role in facilitating memory formation of spatial learning in rats, but the SGK signaling pathway involved in spatial memory formation is not known. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) also plays an important role in memory formation. We therefore examined whether SGK is a downstream target of the MAPK/ERK signaling cascade and whether ERK signaling to SGK mediates spatial memory formation in rats. Results from an in vitro kinase assay revealed that ERK directly phosphorylates SGK at Ser78, but not at Thr256 and Ser422, whereas inhibition of ERK by PD98059 significantly decreased SGK phosphorylation at Ser78, Thr256 and Ser422 following spatial training. Prior administration of PD98059 also antagonized the enhancing effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator that also causes ERK activation, on SGK phosphorylation and cAMP response element binding protein (CREB) phosphorylation. Moreover, TPA-induced SGK phosphorylation and CREB phosphorylation was abolished by prior SGKS78A mutant DNA transfection. By contrast, SGKS78A mutant DNA transfection to hippocampal area CA1 did not affect spatial memory formation, whereas SGKT256A mutant DNA transfection to area CA1 significantly impaired spatial memory formation. ERK was known to regulate sgk mRNA expression, but in the present study we have demonstrated that SGK is also a downstream target of the ERK signaling cascade; ERK directly phosphorylates SGK at Ser78 and indirectly activates SGK at Thr256 and Ser422 through unknown intermediate molecules. Furthermore, ERK activation of SGK is involved in spatial memory formation in rats.
Ching-Tien Lee; Shiaw-Wei Tyan; Yun L Ma; Ming-Chi Tsai; Ying C Yang; Eminy H Y Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  23     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-23     Completed Date:  2006-09-18     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  1311-20     Citation Subset:  IM    
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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MeSH Terms
Cyclic AMP Response Element-Binding Protein / metabolism
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism*
Flavonoids / metabolism
Immediate-Early Proteins / genetics,  metabolism*
MAP Kinase Signaling System / physiology*
Maze Learning / physiology
Memory / physiology*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Rats, Sprague-Dawley
Recombinant Fusion Proteins / genetics,  metabolism
Serine / metabolism
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Cyclic AMP Response Element-Binding Protein; 0/Flavonoids; 0/Immediate-Early Proteins; 0/Recombinant Fusion Proteins; 56-45-1/Serine; EC Kinases; EC regulated kinase; EC Signal-Regulated MAP Kinases

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