The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
A Novel Domain in AMP-Activated Protein Kinase Causes Glycogen Storage Bodies Similar to Those Seen in Hereditary Cardiac Arrhythmias
Open accessAbstract
The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation. Mutations in the gamma2 and gamma3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart and elevated glycogen in pig muscle, respectively. A putative glycogen binding domain (GBD) has now been identified in the beta subunits. Coexpression of truncated beta subunits lacking the GBD with alpha and gamma subunits yielded complexes that were active and normally regulated. However, coexpression of alpha and gamma with full-length beta caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated beta subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with gamma2 mutations.
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“The β-subunit includes a carbohydrate-binding module that grants AMPK to bind to glycogen [25].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [25]
Citations
Cites
AMP‐activated protein kinase: the energy charge hypothesis revisited
Hardie, D. G., & Hawley, S. A. (2001) · BioEssays · doi:10.1002/bies.10009 · Cited by 794
Self-citationA Mutation in PRKAG3 Associated with Excess Glycogen Content in Pig Skeletal Muscle
Milan, D., Jeon, J., Looft, C., Amarger, V., Robic, A., Thelander, M., Rogel-Gaillard, C., Paul, S., Iannuccelli, N., Rask, L., et al. (2000) · Science · doi:10.1126/science.288.5469.1248 · Cited by 733
Identification of a gene responsible for familial Wolff-Parkinson-White syndrome
Gollob, M. H., Green, M. S., Tang, A. S.-L., Gollob, T., Karibe, A., Hassan, A.-S., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106143442403 · Cited by 671
Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding
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Self-citationArad, M., Benson, D. W., Pérez‐Atayde, A. R., McKenna, W. J., Sparks, E. A., Kanter, R. J., McGarry, K., Seidman, J. G., & Seidman, C. E. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14571 · Cited by 545
Blair, E. M. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.11.1215 · Cited by 531
The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., Lenzner, C., Baud, O., Bennoun, M., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16567 · Cited by 499
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Self-citationAMPK β Subunit Targets Metabolic Stress Sensing to Glycogen
Polekhina, G., Gupta, A., Michell, B. J., van Denderen, B., Murthy, S., Feil, S. C., Jennings, I. G., Campbell, D. J., Witters, L. A., Parker, M. W., et al. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00292-6 · Cited by 423
Wojtaszewski, J. F. P., MacDonald, C., Nielsen, J. N., Hellsten, Y., Hardie, D. G., Kemp, B. E., Kiens, B., & Richter, E. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2002 · Cited by 348
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Cited by
Sorted by citations
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Self-citationAMPK: guardian of metabolism and mitochondrial homeostasis
Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,192
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Self-citationAMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Self-citationSteinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,672
Metadata
- Authors
- Hudson, E. R., Pan, D. A., James, J., Lucocq, J. M., Hawley, S. A., Green, K. A., Baba, O., Terashima, T., & Hardie, D. G.
- Affiliations
- University of Dundee (GB)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Hardie, D.Grahame
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 13
- Issue
- 10
- Pages
- 861-866
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2154405414
- Cited by
- 332
- References
- 28
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 8 · 2019: 10 · 2018: 13 · 2017: 10 · 2016: 12 · 2015: 17 · 2014: 16 · 2013: 16 · 2012: 20
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3730 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- Tenovus
- European Commission
- Wellcome Trust (QLG1-CT-2001-01488)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- AMPK, glycogen synthase, protein inclusions, energy homeostasis, kinase overexpression
- MeSH terms
- Arrhythmias, Cardiac, Inclusion Bodies, Glycogen, Glycogen Synthase, Humans, Multienzyme Complexes, Precipitin Tests, Recombinant Fusion Proteins, Protein Serine-Threonine Kinases, Sequence Deletion, Protein Structure, Tertiary, Protein Subunits, Cell Line, Tumor, AMP-Activated Protein Kinases
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