Akt2, but not Akt1, is required for cell survival by inhibiting activation of JNK and p38 after UV irradiation

被引:0
作者
M-A Kim
H-J Kim
H J Jee
A J Kim
Y-S Bae
S S Bae
J Yun
机构
[1] College of Medicine,Department of Biochemistry
[2] Dong-A University,Department of Pharmacology
[3] College of Medicine,undefined
[4] Pusan University,undefined
来源
Oncogene | 2009年 / 28卷
关键词
Akt1; Akt2; isotype-specific function; UV; JNK; p38;
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摘要
The serine/threonine protein kinase, Akt/PKB, has an essential function in cell survival during response to various stresses. Recent studies have demonstrated that Akt isoforms exhibit some distinct physiological functions, but the isotype-specific functions for Akt in the stress response have not been fully identified. In this study, we analysed the cellular response to genotoxic stress using isogenic wild-type, Akt1−/− and Akt2−/− mouse embryonic fibroblasts (MEFs). Marked hypersensitivity of Akt2−/− MEFs was observed to UV irradiation, whereas wild-type and Akt1−/− MEFs showed comparable levels of resistance. Akt2−/− mouse aortic endothelial cells also showed hypersensitivity to UV and the reconstitution of Akt2 expression in the Akt2−/− MEFs restored the UV resistance of the cells. Interestingly, upon UV irradiation, JNK and p38 were significantly upregulated in Akt2−/− MEFs, compared to wild-type and Akt1−/− MEFs. Additionally, inhibition of JNK and p38 activation reduced UV-induced cell death. Furthermore, both the hyperactivation of JNK and p38 and the UV-induced cell death in Akt2−/− MEFs were completely inhibited by restoring Akt2 expression. These results indicate that Akt2, but not Akt1, is essential for cell survival upon UV irradiation, and that Akt2 prevents UV-induced cell death by inhibiting activation of JNK and p38.
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页码:1241 / 1247
页数:6
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