Control of mammalian glycogen synthase by PAS kinase.
The regulation of glycogen metabolism is critical for the maintenance of glucose and energy homeostasis in mammals. Glycogen synthase, the enzyme responsible for glycogen production, is regulated by multisite phosphorylation in yeast and mammals. We have previously identified PAS kinase as a physiological regulator of glycogen synthase in Saccharomyces cerevisiae. We provide evidence here that PAS kinase is an important regulator of mammalian glycogen synthase. Glycogen synthase is efficiently phosphorylated by PAS kinase in vitro at Ser-640, a known regulatory phosphosite. Efficient phosphorylation requires a region of PAS kinase outside the catalytic domain. This region appears to mediate a direct interaction between glycogen synthase and PAS kinase, thereby targeting kinase activity to this substrate specifically. This interaction is regulated by the PAS kinase PAS domain, raising the possibility that this interaction (and phosphorylation event) is modulated by the cellular metabolic state. This mode of regulation provides a mechanism for metabolic status to impinge directly on the cellular decision of whether to store or use available energy.
Wilson
Wayne A
WA
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Skurat
Alexander V
AV
Probst
Brandon
B
de Paoli-Roach
Anna
A
Roach
Peter J
PJ
Rutter
Jared
J
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D006003:Glycogen / Q000494:pharmacology; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008322:Mammals; D009132:Muscles / Q000201:enzymology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013379:Substrate Specificity
D006657:Histones; D006003:Glycogen; D006006:Glycogen Synthase; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases