AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase
Autor: | Monique Beullens, Bruno Guigas, Alexander von Wilamowitz-Moellendorff, Mark H. Rider, Kei Sakamoto, Liliane Maisin, Joan J. Guinovart, Louis Hue, Nusrat Hussain, Didier Vertommen, Marc Foretz, Benoit Viollet, Laurent Bultot |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Male
Liver cytology Enzyme Activators Thiophenes macromolecular substances AMP-Activated Protein Kinases Biochemistry Glucagon law.invention Mice AMP-activated protein kinase glycogen synthase law AMP-activated protein kinase (AMPK) Consensus Sequence hepatocyte Animals Humans Amino Acid Sequence Phosphorylation Rats Wistar Protein kinase A Glycogen synthase Molecular Biology Cells Cultured Mice Knockout biology Chemistry A769662 Biphenyl Compounds Apraxia Ideomotor AMPK Cell Biology Ribonucleotides Aminoimidazole Carboxamide Cyclic AMP-Dependent Protein Kinases Molecular biology 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICA riboside) Rats Enzyme Activation carbohydrates (lipids) Liver glucagon Pyrones Hepatocytes Recombinant DNA biology.protein Protein Processing Post-Translational |
Zdroj: | Biochemical Journal, 443, 193-203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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