1. Academic Validation
  2. AMPK is a direct adenylate charge-regulated protein kinase

AMPK is a direct adenylate charge-regulated protein kinase

  • Science. 2011 Jun 17;332(6036):1433-5. doi: 10.1126/science.1200094.
Jonathan S Oakhill 1 Rohan Steel Zhi-Ping Chen John W Scott Naomi Ling Shanna Tam Bruce E Kemp
Affiliations

Affiliation

  • 1 Department of Protein Chemistry and Metabolism, St. Vincent's Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Victoria, Australia. [email protected]
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 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 contrast to AMP, ADP did not directly activate phosphorylated AMPK. In this way, both ADP/ATP and AMP/ATP ratios contribute to AMPK regulation.

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