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The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression.
Cao, Yonghao; Li, Hai; Liu, Haifeng; Zheng, Chao; Ji, Hongbin; Liu, Xiaolong.
Afiliação
  • Cao Y; Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Cell Res ; 20(1): 99-108, 2010 Jan.
Article em En | MEDLINE | ID: mdl-20029389
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 Bcl-XL. Importantly, ectopic expression of either Bcl-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 Bcl-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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Transdução de Sinais / Proteínas Serina-Treonina Quinases / Proteína bcl-X / Proteínas Quinases Ativadas por AMP Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Res Ano de publicação: 2010 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Transdução de Sinais / Proteínas Serina-Treonina Quinases / Proteína bcl-X / Proteínas Quinases Ativadas por AMP Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Res Ano de publicação: 2010 Tipo de documento: Article País de afiliação: China