Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation

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The protein serine-threonine kinase Akt mediates cell survival signaling initiated by various growth-promoting factors such as insulin. Here we report that SEK1 is a target of Akt in intact cells. Insulin inhibited the anisomycin-induced stimulation of both endogenous SEK1 and its substrate c-Jun N-terminal kinase (JNK), but not that of the upstream kinase MEKK1, in 293T cells. The inhibitory action of insulin on SEK1 or JNK1 activation was prevented by the phosphatidylinositol 3-kinase inhibitor LY294002. Expression of a constitutively active form of Akt also inhibited both SEK1 and JNK1 activation, but not that of MEKK1, in transfected 293T cells. Co-immunoprecipitation analysis revealed that endogenous Akt physically interacted with endogenous SEK1 in cells and that this interaction was promoted by insulin. In vitro and in vivo P-32 labeling indicated that Akt phosphorylated SEK1 on serine 78. The SEK1 mutant SEK1(S78A) was resistant to Akt-induced inhibition. Finally, activated Akt inhibited SEK1-mediated apoptosis, and this effect of Akt was prevented by overexpression of SEK(S78A). Taken together, these results suggest that Akt suppresses stress-activated signaling by targeting SEK1.
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Issue Date
2002
Language
English
Article Type
Article
Keywords

N-TERMINAL KINASE; C-JUN; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; PHOSPHOINOSITIDE 3-KINASE; CELL-SURVIVAL; ACTIVATION; JNK; PATHWAY; EXPRESSION

Citation

JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.4, pp.2573 - 2578

ISSN
0021-9258
DOI
10.1074/jbc.M110299200
URI
http://hdl.handle.net/10203/78957
Appears in Collection
BS-Journal Papers(저널논문)
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