ArticleThe Biochemical journal2024
AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand.
Article in The Biochemical journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 13 citations in OpenAlex.
- A conserved archaeal protein with evolutionary links to bacterial ribosome hibernation and eukaryotic energy sensing.The EMBO journal · 2026Article
- AMPK phosphorylation proceeds through hierarchical proteoform cascades revealed by integrated mass spectrometry.Science advances · 2026Article
- AMPK-mediated modulation of JAK2/STAT3 signaling in asthma: a promising target for controlling airway inflammation and remodeling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.Molecular biology reports · 2026Review
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- Molecular mechanisms of SIRT1 in regulating ageing and related intervention strategies.Molecular biology reports · 2026Review
- The role of metabolic reprogramming in oocyte development: research progress and prospects.Frontiers in reproductive health · 2026Review
- Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827.Science advances · 2025Article
- Whey Protein Mitigates Oxidative Stress Injury and Improves Protein Synthesis in Mouse Skeletal Muscle by Regulating the SIRT1/Nrf2/HO-1 Axis and AMPK/TSC2/mTOR/4EBP1 Pathway.Journal of food science · 2025Article
- The Hepatic Axis Fructose-Methylglyoxal-AMPK: Starring or Secondary Role in Chronic Metabolic Disease?Journal of clinical medicine · 2025Article
- Assays of Different Mechanisms of AMPK Activation, and Use of Cells Expressing Mutant AMPK to Delineate Activation Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Research progress on AMPK in the pathogenesis and treatment of MASLD.Frontiers in immunology · 2025Review
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- The pro-drug C13 activates AMPK by two distinct mechanisms.The Biochemical journal · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. When activated by increases in ADP:ATP and/or AMP:ATP ratios (signalling energy deficit), AMPK acts to restore energy balance. Binding of AMP to one or more of three CBS repeats (CBS1, CBS3, CBS4) on the AMPK-γ subunit activates the kinase complex by three complementary mechanisms: (i) promoting α-subunit Thr172 phosphorylation by the upstream kinase LKB1; (ii) protecting against Thr172 dephosphorylation; (iii) allosteric activation. Surprisingly, binding of ADP has been reported to mimic the first two effects, but not the third. We now show that at physiologically relevant concentrations of Mg.ATP2- (above those used in the standard assay) ADP binding does cause allosteric activation. However, ADP causes only a modest activation because (unlike AMP), at concentrations just above those where activation becomes evident, ADP starts to cause competitive inhibition at the catalytic site. Our results cast doubt on the physiological relevance of the effects of ADP and suggest that AMP is the primary activator in vivo. We have also made mutations to hydrophobic residues involved in binding adenine nucleotides at each of the three γ subunit CBS repeats of the human α2β2γ1 complex and examined their effects on regulation by AMP and ADP. Mutation of the CBS3 site has the largest effects on all three mechanisms of AMP activation, especially at lower ATP concentrations, while mutation of CBS4 reduces the sensitivity to AMP. All three sites appear to be required for allosteric activation by ADP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.