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AMP-activated protein kinase: also regulated by ADP?
Abstract
AMPK is a ubiquitous sensor of cellular energy status in eukaryotic cells. It is activated by stresses causing ATP depletion and, once activated, maintains energy homeostasis by phosphorylating targets that activate catabolism and inhibit energy-consuming processes. Evidence derived from non-mammalian orthologs suggests that its ancestral role was in the response to starvation for a carbon source. We review recent findings showing that AMPK is activated by ADP as well as AMP, and discuss the mechanism by which binding of these nucleotides prevent its dephosphorylation and inactivation. We also discuss the role of the carbohydrate-binding module on the β subunit and the mechanisms by which it is activated by drugs and xenobiotics such as metformin and resveratrol.
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“Binding of AMP, and to a lesser degree ADP, to the γ-subunit stimulates AMPK activity via three mechanisms [27,28,29].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [27]
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Metadata
- Authors
- Hardie, D. G., Carling, D., & Gamblin, S. J.
- Affiliations
- University of Dundee (GB)
- Imperial College London (GB)
- Corresponding author
- Hardie, D. Grahame
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 36
- Issue
- 9
- Pages
- 470-477
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2107227663
- Cited by
- 187
- References
- 81
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 16 · 2019: 9 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 13 · 2013: 26 · 2012: 26
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- 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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- AMPK, ADP stimulation, energy sensing, energy homeostasis, carbohydrate-binding module, metformin, resveratrol, starvation response, nucleotide binding
- MeSH terms
- Resveratrol, Adenosine Diphosphate, Adenosine Monophosphate, Adenosine Triphosphate, Animals, Binding Sites, Electron Transport, Energy Metabolism, Enzyme Activation, Fungal Proteins, Glucose, Glycogen, Humans, Metformin, Mitochondria, Phosphorylation, Protein Conformation, Stilbenes, Transcription, Genetic, Yeasts, AMP-Activated Protein Kinases
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