Cited by 612Metabolism, Diabetes, and CancerBiochemical and Molecular ResearchProtein Kinase Regulation and GTPase Signaling

AMPK is a direct adenylate charge-regulated protein kinase

Oakhill, Jonathan S., Steel, Rohan, Chen, Zhi-Ping, Scott, John W., Ling, Naomi, Tam, Shanna, Kemp, Bruce E.·2011·Science

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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Crossref · 10.1126/science.1200094

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Authors
Oakhill, J. S., Steel, R., Chen, Z.-P., Scott, J. W., Ling, N., Tam, S., & Kemp, B. E.
Affiliations
  • The University of Melbourne (AU)
  • Department of Protein Chemistry and Metabolism, St. Vincent’s Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Victoria, Australia.
Corresponding author
Oakhill, Jonathan S.
Venue
Science
Published
2011-06-17
Volume
332
Issue
6036
Pages
1433-1435
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2080107084
Cited by
612
References
27
Citations by year
2026: 25 · 2025: 25 · 2024: 34 · 2023: 27 · 2022: 34 · 2021: 37 · 2020: 34 · 2019: 31 · 2018: 42 · 2017: 51 · 2016: 32 · 2015: 48 · 2014: 52 · 2013: 60 · 2012: 59
FWCI
24.64
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Research Bank (Australian Catholic University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
AMPK, AMPK activation, energy balance, adenosine triphosphate, adenosine diphosphate, AMP, adenosine, Thr172 phosphorylation, LKB1, CaMKKβ, allosteric regulation, kinase regulation
MeSH terms
Adenosine Diphosphate, Adenosine Monophosphate, Adenosine Triphosphate, Animals, Binding Sites, Chlorocebus aethiops, Enzyme Activation, Phosphorylation, Recombinant Fusion Proteins, Threonine, Protein Serine-Threonine Kinases, COS Cells, Myristic Acid, Protein Subunits, Calcium-Calmodulin-Dependent Protein Kinase Kinase, AMP-Activated Protein Kinases

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