AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase
Top Cited Papers
- 16 June 2011
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 332 (6036), 1433-1435
- https://doi.org/10.1126/science.1200094
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 (Thr172) by kinases LKB1 or CaMKKβ, and this is promoted by AMP binding to the γ subunit. AMP sustains activity by inhibiting dephosphorylation of α-Thr172, whereas ATP promotes dephosphorylation. Adenosine diphosphate (ADP), like AMP, bound to γ 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.This publication has 28 references indexed in Scilit:
- Structure of mammalian AMPK and its regulation by ADPNature, 2011
- β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK)Proceedings of the National Academy of Sciences, 2010
- Structural Insight into AMPK Regulation: ADP Comes into PlayStructure, 2007
- AMP-activated/SNF1 protein kinases: conserved guardians of cellular energyNature Reviews Molecular Cell Biology, 2007
- Structural basis for AMP binding to mammalian AMP-activated protein kinaseNature, 2007
- 5′‐AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP‐activated protein kinase. Studies using bacterially expressed human protein phosphatase‐2Cα and native bovine protein phosphatase‐2AcFEBS Letters, 1995
- Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exerciseActa Physiologica Scandinavica, 1989
- ATP and IMP in single human muscle fibres after high intensity exerciseClinical Physiology and Functional Imaging, 1987
- Muscular fatigue investigated by phosphorus nuclear magnetic resonanceNature, 1978
- The amount and compartmentalization of adenosine diphosphate in muscleBiochimica et Biophysica Acta, 1962