AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase
Research output: Contribution to journal › Journal article › Research › peer-review
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 Ser 7, 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 Ser 7 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 Ser 7 phosphorylation.
Original language | English |
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Journal | Biochemical Journal |
Volume | 443 |
Issue number | 1 |
Pages (from-to) | 193-203 |
Number of pages | 11 |
ISSN | 0264-6021 |
DOIs | |
Publication status | Published - 1 Apr 2012 |
Externally published | Yes |
- 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICA riboside), A769662, AMP-activated protein kinase (AMPK), Glucagon, Glycogen synthase, Hepatocyte
Research areas
ID: 239567593