Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding
Open accessAbstract
The AMP-activated protein kinase (AMPK) cascade plays an important role in the regulation of energy homeostasis within the cell. AMPK is a heterotrimer composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma). We have isolated and characterized two isoforms of the gamma subunit, termed gamma2 and gamma3. Both gamma2 (569 amino acids) and gamma3 (492 amino acids) have a long N-terminal domain which is not present in the previously characterized isoform, gamma1. As with gamma1, mRNA encoding gamma2 is widely expressed in human tissues, whereas significant expression of gamma3 mRNA was only detected in skeletal muscle. Using isoform-specific antibodies, we determined the AMPK activity associated with the different gamma isoforms in a number of rat tissues. In most tissues examined more than 80% of total AMPK activity was associated with the gamma1 isoform, with the remaining activity being accounted for mainly by the gamma2 isoform. Exceptions to this were testis and, more notably, brain where all three isoforms contributed approximately equally to activity. There was no evidence for any selective association between the alpha1 and alpha2isoforms and the various gamma isoforms. However, the AMP-dependence of the kinase complex is markedly affected by the identity of the gamma isoform present, with gamma2-containing complexes having the greatest AMP-dependence, gamma3 the lowest, and gamma1 having an intermediate effect. Labelling studies, using the reactive AMP analogue 8-azido-[(32)P]AMP, indicate that the gamma subunit may participate directly in the binding of AMP within the complex.
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In humans, each AMPK subunit has multiple distinct isoforms encoded by different genes: α1 and α2 by PRKAA1 and PRKAA2; β1 and β2 by PRKAB1 and PRKAB2; γ1, γ2, and γ3 by PRKAG1, PRKAG2, and PRKAG3.
“In humans, each subunit has multiple distinct isoforms encoded by different genes: the α-subunit has two isoforms, α1 and α2, encoded by gene PRKAA1 and PRKAA2, respectively [20]; the β-subunit has two isoforms, β1 and β2, encoded by gene PRKAB1 and PRKAB2, respectively [21]; and the γ-subunit has three isoforms, γ1, γ2, and γ3, encoded by gene PRKAG1, PRKAG2, and PRKAG3, respectively [22].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [22]
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- Authors
- CHEUNG, P. C. F., SALT, I. P., DAVIES, S. P., HARDIE, D. G., & CARLING, D.
- Affiliations
- Hammersmith Hospital (GB)
- University of Dundee (GB)
- Corresponding author
- CARLING, David
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2000-03-07
- Volume
- 346
- Issue
- 3
- Pages
- 659-669
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1220898
- OpenAlex
- W2083655799
- Cited by
- 637
- References
- 37
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 17 · 2023: 12 · 2022: 24 · 2021: 17 · 2020: 19 · 2019: 18 · 2018: 22 · 2017: 27 · 2016: 34 · 2015: 26 · 2014: 27 · 2013: 30 · 2012: 29
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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, AMP binding, N-terminal domain, energy homeostasis, skeletal muscle, brain, testis
- MeSH terms
- Adenosine Monophosphate, Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Humans, Male, Molecular Sequence Data, Precipitin Tests, Protein Binding, Protein Kinases, Blotting, Northern, Sequence Homology, Amino Acid, DNA, Complementary, Protein Isoforms, Rats, AMP-Activated Protein Kinases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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