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LKB 1 and AMPK : central regulators of lymphocyte metabolism and function

2012/08/14 by Julianna Blagih, Connie M. Krawczyk, Russell G. Jones

paper · doi:10.1111/j.1600-065x.2012.01157.x

Abstract

Summary When T cells encounter foreign antigen and appropriate costimulatory signals from professional antigen‐presenting cells ( APC s), they initiate a coordinated program of rapid proliferation and differentiation, leading to the development of activated T cells with specific effector functions tailored toward pathogen clearance or control. One of the fundamental programs that underpin T ‐cell proliferation and function is the regulation of cellular metabolism. Recent efforts to identify the signal transduction pathways that regulate T ‐cell metabolism have led to the identification of liver kinase B1 ( LKB 1) and AMP ‐activated protein kinase ( AMPK ) as key regulators of T ‐cell metabolism. LKB 1 and AMPK are part of an evolutionarily conserved signal transduction pathway that monitors cellular energy status. AMPK senses bioenergetic fluctuations in cells and works in concert with LKB 1 to maintain cellular energy homeostasis by promoting catabolic pathways of ATP production and limiting processes that consume ATP . Recent data indicate that LKB 1 and AMPK can influence diverse aspects of T ‐cell biology beyond metabolism, including T ‐cell development, peripheral T ‐cell homeostasis, and T ‐cell effector function. In this review, we focus on the regulation of lymphocyte metabolism by this energy‐sensing pathway and discuss its influence on T ‐cell function.

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