Cited by 132Metabolism, Diabetes, and CancerGlycogen Storage Diseases and MyoclonusBiochemical and Molecular Research

AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase

Bultot, Laurent, Guigas, Bruno, Von Wilamowitz-Moellendorff, Alexander, Maisin, Liliane, Vertommen, Didier, Hussain, Nusrat, Beullens, Monique, Guinovart, Joan J. +5 more·2012·Biochemical Journal

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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Crossref · 10.1042/bj20112026

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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.

    “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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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
Venue
Biochemical Journal
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
  • Health Sciences › Medicine › Rheumatology › 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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