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 language | English |
|---|---|
| Pages (from-to) | 2573-2578 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2002 Jan 25 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation
AU - Park, Hee Sae
AU - Kim, Mi Sung
AU - Huh, Sung Ho
AU - Park, Jihyun
AU - Chung, Jongkyeong
AU - Kang, Sang Sun
AU - Choi, Eui Ju
PY - 2002/1/25
Y1 - 2002/1/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037169526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037169526&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110299200
DO - 10.1074/jbc.M110299200
M3 - Article
C2 - 11707464
AN - SCOPUS:0037169526
VL - 277
SP - 2573
EP - 2578
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 4
ER -