ArticleThe Biochemical journal2016
Probing the enzyme kinetics, allosteric modulation and activation of α1- and α2-subunit-containing AMP-activated protein kinase (AMPK) heterotrimeric complexes by pharmacological and physiological activators.
Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
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- EDIL3/Del-1-Dependent Induction of AMPKβ Phosphorylation Regulates the Progression of Mesenchymal Stem-like Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- An enzyme-linked immunosorbent assay (ELISA)-based activity assay for AMP-activated protein kinase (AMPK).FEBS open bio · 2025Article
- Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.Journal of medicinal chemistry · 2025Review
- AMPK phosphosite profiling by label-free mass spectrometry reveals a multitude of mTORC1-regulated substrates.npj metabolic health and disease · 2025Article
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.Genes & diseases · 2024Review
- The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects.Heliyon · 2024Review
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand.The Biochemical journal · 2024Article
- The role of AMPK in macrophage metabolism, function and polarisation.Journal of translational medicine · 2023Review
- The Role of PKGIα and AMPK Signaling Interplay in the Regulation of Albumin Permeability in Cultured Rat Podocytes.International journal of molecular sciences · 2023Article
- AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension.International journal of molecular sciences · 2022Review
- Natural (dihydro)phenanthrene plant compounds are direct activators of AMPK through its allosteric drug and metabolite-binding site.The Journal of biological chemistry · 2022Article
- A Modular Mathematical Model of Exercise-Induced Changes in Metabolism, Signaling, and Gene Expression in Human Skeletal Muscle.International journal of molecular sciences · 2021Article
- Direct small molecule ADaM-site AMPK activators reveal an AMPKγ3-independent mechanism for blood glucose lowering.Molecular metabolism · 2021Article
- Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle.Molecular metabolism · 2021Article
- Mechanisms of Inhibition of Excessive Microglial Activation by Melatonin.Journal of molecular neuroscience : MN · 2020Review
- ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise.PLoS computational biology · 2020Article
- Isoform-specific roles of AMPK catalytic α subunits in Alzheimer's disease.The Journal of clinical investigation · 2020Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that serves as a pleotropic regulator of whole body energy homoeostasis. AMPK exists as a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), each present as multiple isoforms. In the present study, we compared the enzyme kinetics and allosteric modulation of six recombinant AMPK isoforms, α1β1γ1, α1β2γ1, α1β2γ3, α2β1γ1, α2β2γ1 and α2β2γ3 using known activators, A769662 and AMP. The α1-containing complexes exhibited higher specific activities and lower Km values for a widely used peptide substrate (SAMS) compared with α2-complexes. Surface plasmon resonance (SPR)-based direct binding measurements revealed biphasic binding modes with two distinct equilibrium binding constants for AMP, ADP and ATP across all isoforms tested. The α2-complexes were ∼25-fold more sensitive than α1-complexes to dephosphorylation of a critical threonine on their activation loop (pThr(172/174)). However, α2-complexes were more readily activated by AMP than α1-complexes. Compared with β1-containing heterotrimers, β2-containing AMPK isoforms are less sensitive to activation by A769662, a synthetic activator. These data demonstrate that ligand induced activation of AMPK isoforms may vary significantly based on their AMPK subunit composition. Our studies provide insights for the design of isoform-selective AMPK activators for the treatment of metabolic diseases.
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