Cited by 637Metabolism, Diabetes, and CancerBiochemical and Molecular ResearchProtein Kinase Regulation and GTPase Signaling

Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding

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CHEUNG, Peter C. F., SALT, Ian P., DAVIES, Stephen P., HARDIE, D. Grahame, CARLING, David·2000·Biochemical Journal

Abstract

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
Published
2000-03-07
Volume
346
Issue
3
Pages
659-669
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
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
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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