TY - JOUR T1 - AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase A1 - Bultot,Laurent A1 - Guigas,Bruno A1 - Von Wilamowitz-Moellendorff,Alexander A1 - Maisin,Liliane A1 - Vertommen,Didier A1 - Hussain,Nusrat A1 - Beullens,Monique A1 - Guinovart,Joan J. A1 - Foretz,Marc A1 - Viollet,Benoit A1 - Sakamoto,Kei A1 - Hue,Louis A1 - Rider,Mark H. AU - Bultot,Laurent AU - Guigas,Bruno AU - Von Wilamowitz-Moellendorff,Alexander AU - Maisin,Liliane AU - Vertommen,Didier AU - Hussain,Nusrat AU - Beullens,Monique AU - Guinovart,Joan J. AU - Foretz,Marc AU - Viollet,Benoit AU - Sakamoto,Kei AU - Hue,Louis AU - Rider,Mark H. PY - 2012/4/1 Y1 - 2012/4/1 N2 -

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-beta-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 alpha 1/alpha 2 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.

AB -

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-beta-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 alpha 1/alpha 2 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.

U2 - 10.1042/BJ20112026 DO - 10.1042/BJ20112026 M1 - Article JO - Biochemical Journal JF - Biochemical Journal SN - 0264-6021 VL - 443 SP - 193 EP - 203 ER -