The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression  

作　　者：Yonghao Cao Hai Li Haifeng Liu Chao Zheng Hongbin Ji Xiaolong Liu 

机构地区：[1]Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Cell Research》2010年第1期99-108,共10页细胞研究（英文版）

基　　金：Acknowledgments We thank X Wu （Fudan University） for LckCre mouse and K Wong （Dana-Farber Cancer Institute） for LKB1 mouse, R Bosselut （National Institutes of Health） and D Li （Shanghai Institutes for Biological Sciences） for instructive comments on the manuscript; We are grateful to our colleagues F Liu for animal husbandry, W Bian for cell sorting and X Wang for real-time PCR analysis. This research was supported in part by the National Natural Science Foundation of China （30872290, 30925031）, the Ministry of Science and Technology （2006CB504303, 2007CB815802, 2009ZX 10004-105）, the Hi-Tech Research and Development Program of China （2007AA02Z167）, the National Basic Research Program of China （2007CB914504） and the Chinese Academy of Sciences （KSCX 1-YW-R-43, KSCX2-YW-R-10）.

摘　　要：LKB1 is a serine/threonine kinase that directly activates the energy sensor AMP-activated protein kinase （AMPK） in response to bioenergetic stress, and mainly acts as a tumor suppressor that controls cell polarity and proliferation. Although LKB1 is expressed in multiple tissues including the thymus and the spleen, its roles in T-cell development and function remain unknown. Here, we show that T-cell-specific deletion of LKB1 resulted in reduced survival of double-positive （DP） thymocytes and impaired generation of both CD4 and CD8 single-positive thymocytes. Disruption of LKB1 not only prevented the activation of AMPK but also impaired the expression of anti-apoptotic protein BcI-XL. Importantly, ectopic expression of either BcI-XL or the constitutively active AMPK mutant significantly rescued DP thymocytes from LKB1 deficiency-induced cell death. Moreover, ectopic expression of the constitutively active AMPK mutant was found to restore the expression of BcI-XL in LKB1-deficient DP thymocytes. These findings identify LKB1 as a critical factor for the survival of DP thymocytes through regulation of AMPK activation and Bcl-XL expression.

关 键 词：LKB 1 AMPK BCL-XL THYMOCYTE SURVIVAL development 

分 类 号：Q257[生物学—细胞生物学] S831.1[农业科学—畜牧学]