Identification of a Novel AMP-activated Protein Kinase β Subunit Isoform That Is Highly Expressed in Skeletal Muscle
Open accessAbstract
The AMP-activated protein kinase (AMPK) is a member of a growing family of related kinases, including the SNF1 complex in yeast, which respond to nutritional stress. AMPK is a heterotrimeric complex of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), and proteins related to all three subunits have been identified in the SNF1 complex. We have used the two-hybrid system in order to identify proteins interacting with the catalytic subunit (alpha2). Using this approach, we have isolated a novel AMPKbeta isoform, which we designate AMPKbeta2. The N-terminal region of beta2 differs significantly from that of the previously characterized isoform (beta1), suggesting that this region could play a role in isoform-specific AMPK activity. Comparison of the C-terminal sequences of beta1 and beta2 with their related proteins in yeast identifies two highly conserved regions predicted to be involved in binding of the alpha and gamma subunits. The expression of beta1 and beta2 was examined in a number of tissues, revealing that the beta1 isoform is highly expressed in liver with low expression in skeletal muscle, whereas the opposite pattern is observed for the beta2 isoform. These results suggest that the beta isoforms have tissue-specific roles, which may involve altered responses to upstream signaling and/or downstream targeting of the AMPK 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 [21]
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- Authors
- Thornton, C., Snowden, M. A., & Carling, D.
- Affiliations
- Hammersmith Hospital (GB)
- Corresponding author
- Carling, David
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 273
- Issue
- 20
- Pages
- 12443-12450
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1983834588
- Cited by
- 240
- References
- 32
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 15 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 14
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- 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, skeletal muscle, tissue-specific gene expression, N-terminal domain, protein-protein interaction, liver, nutritional stress
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Humans, Molecular Sequence Data, Multienzyme Complexes, Protein Kinases, Blotting, Western, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Muscle, Skeletal, AMP-Activated Protein Kinases
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