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.; Foretz, Marc; Viollet, Benoit; Sakamoto, Kei; Hue, Louis; Rider, Mark H.
In: Biochemical Journal, Vol. 443, 01.04.2012, p. 193-203.Research output: Contribution to journal › Article
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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 - <p>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.</p>
AB - <p>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.</p>
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 -