Journal article

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

Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2011


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 αβγ 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 (Thr(172)) by kinases LKB1 or CaMKKβ, and this is promoted by AMP binding to the γ subunit. AMP sustains activity by inhibiting dephosphorylation of α-Thr(172), whereas ATP promotes dephosphorylation. Adenosine diphosphate (ADP), like AMP, bound to γ sites 1 and 3 and stimulated α-Thr(172) phosphorylation. However, in con..

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University of Melbourne Researchers


Funding Acknowledgements

We thank F. Katsis for the preparation of antibodies and L. Macaulay at Commonwealth Scientific and Industrial Research Organisation Parkville, Victoria, Australia, for CaMKK beta expression constructs. We are most grateful to S. Gamblin and D. Carling and their colleagues at Medical Research Council National Institute of Medical Research and Hammersmith Hospital, respectively, for generously sharing with us the observation that ADP inhibited the dephosphorylation of AMPK by PP2c (30), which prompted us to test whether ADP also controlled the kinase kinase reaction. This work was supported by grants from the Australian Research Council, the National Health and Medical Research Council (NHMRC), and the Victorian Government Operational Infrastructure Support Scheme. B. E. K. is an NHMRC Fellow.