PubMed Journals: J Biol Chem
Source: PMID: 11707464
⇦ ⇨ J Biol Chem. 2002 Jan 25;277(4):2573-8.
⇩ Epub 2001 Nov 13.
Akt (protein kinase B) negatively regulates
SEK1 by means of protein phosphorylation.
Park HS(1), Kim MS, Huh SH, Park J, Chung
J, Kang SS, Choi EJ.
(1) National Creative Research Initiative
Center for Cell Death, Graduate School of
Biotechnology, Korea University, Seoul 136-701,
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 (32)P 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
DOI: 10.1074/jbc.M110299200 PMID: 11707464
[Indexed for MEDLINE]