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Science 332 (6036): 1433-1435

Copyright © 2011 by the American Association for the Advancement of Science

AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase

Jonathan S. Oakhill,* Rohan Steel, Zhi-Ping Chen, John W. Scott, Naomi Ling, Shanna Tam, Bruce E. Kemp

Abstract: The adenosine monophosphate (AMP)–activated protein kinase (AMPK) regulates whole-body and cellular energy balance in response to energy demand and supply. AMPK is an αβ{gamma} heterotrimer activated by decreasing concentrations of adenosine triphosphate (ATP) and increasing AMP concentrations. AMPK activation depends on phosphorylation of the α catalytic subunit on threonine-172 (Thr172) by kinases LKB1 or CaMKKβ, and this is promoted by AMP binding to the {gamma} subunit. AMP sustains activity by inhibiting dephosphorylation of α-Thr172, whereas ATP promotes dephosphorylation. Adenosine diphosphate (ADP), like AMP, bound to {gamma} sites 1 and 3 and stimulated α-Thr172 phosphorylation. However, in contrast to AMP, ADP did not directly activate phosphorylated AMPK. In this way, both ADP/ATP and AMP/ATP ratios contribute to AMPK regulation.

Department of Protein Chemistry and Metabolism, St. Vincent’s Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Victoria, Australia.

* To whom correspondence should be addressed. E-mail: joakhill{at}

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