The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase
Abstract
Recombinant muscle GYS1 (glycogen synthase 1) and recombinant liver GYS2 were phosphorylated by recombinant AMPK (AMP-activated protein kinase) in a time-dependent manner and to a similar stoichiometry. The phosphorylation site in GYS2 was identified as Ser7, which lies in a favourable consensus for phosphorylation by AMPK. Phosphorylation of GYS1 or GYS2 by AMPK led to enzyme inactivation by decreasing the affinity for both UDP-Glc (UDP-glucose) [assayed in the absence of Glc-6-P (glucose-6-phosphate)] and Glc-6-P (assayed at low UDP-Glc concentrations). Incubation of freshly isolated rat hepatocytes with the pharmacological AMPK activators AICA riboside (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) or A769662 led to persistent GYS inactivation and Ser7 phosphorylation, whereas inactivation by glucagon treatment was transient. In hepatocytes from mice harbouring a liver-specific deletion of the AMPK catalytic α1/α2 subunits, GYS2 inactivation by AICA riboside and A769662 was blunted, whereas inactivation by glucagon was unaffected. The results suggest that GYS inactivation by AMPK activators in hepatocytes is due to GYS2 Ser7 phosphorylation.
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“In liver, GS inactivation by AMPK activators (AICAR and A769662) occurs at S7 phosphorylation site on GS2, which is the liver-specific isoform [136].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [136]
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Cites
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Self-citationUse of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
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Metadata
- Authors
- Bultot, L., Guigas, B., Von Wilamowitz-Moellendorff, A., Maisin, L., Vertommen, D., Hussain, N., Beullens, M., Guinovart, J. J., Foretz, M., Viollet, B., Sakamoto, K., Hue, L., & Rider, M. H.
- Affiliations
- de Duve Institute (BE)
- Leiden University Medical Center (NL)
- MRC Protein Phosphorylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
- KU Leuven (BE)
- Institute for Research in Biomedicine (ES)
- Centre National de la Recherche Scientifique (FR)
- INSERM U1016, Institut Cochin, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France
- University of Dundee (GB)
- Corresponding author
- Bultot, Laurent
- Maisin, Liliane
- Vertommen, Didier
- Hussain, Nusrat
- Hue, Louis
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2012-03-14
- Volume
- 443
- Issue
- 1
- Pages
- 193-203
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2075032036
- Cited by
- 131
- References
- 54
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 5 · 2017: 13 · 2016: 8 · 2015: 13 · 2014: 4 · 2013: 10 · 2012: 5
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Lirias (submittedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- AMPK, glycogen synthase, glycogen synthase 1, enzyme inactivation, liver glycogen metabolism, hepatocytes, AICA riboside, A769662, glucagon, UDP-glucose, glucose-6-phosphate
- MeSH terms
- Amino Acid Sequence, Aminoimidazole Carboxamide, Animals, Biphenyl Compounds, Cells, Cultured, Enzyme Activation, Glycogen Synthase, Humans, Liver, Male, Phosphorylation, Protein Processing, Post-Translational, Pyrones, Ribonucleotides, Thiophenes, Consensus Sequence, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Apraxia, Ideomotor, Enzyme Activators, Hepatocytes, Mice, Rats, AMP-Activated Protein Kinases
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