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

Hee Sae Park, Mi Sung Kim, Sung Ho Huh, Jihyun Park, Jongkyeong Chung, Sang Sun Kang, Eui Ju Choi

Research output: Contribution to journalArticle

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Abstract

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 32P 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.

Original languageEnglish
Pages (from-to)2573-2578
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
Publication statusPublished - 2002 Jan 25

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Proto-Oncogene Proteins c-akt
Phosphorylation
Insulin
HEK293 Cells
Proteins
Chemical activation
Anisomycin
Phosphatidylinositol 3-Kinase
Cell signaling
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
JNK Mitogen-Activated Protein Kinases
Protein-Serine-Threonine Kinases
Immunoprecipitation
Cell Communication
Labeling
Serine
Cell Survival
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation. / Park, Hee Sae; Kim, Mi Sung; Huh, Sung Ho; Park, Jihyun; Chung, Jongkyeong; Kang, Sang Sun; Choi, Eui Ju.

In: Journal of Biological Chemistry, Vol. 277, No. 4, 25.01.2002, p. 2573-2578.

Research output: Contribution to journalArticle

Park, Hee Sae ; Kim, Mi Sung ; Huh, Sung Ho ; Park, Jihyun ; Chung, Jongkyeong ; Kang, Sang Sun ; Choi, Eui Ju. / Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 4. pp. 2573-2578.
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