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
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
Externí odkaz: