Amino acid sequences at the two sites on glycogen synthetase phosphorylated by cyclic AMP-dependent protein kinase and their dephosphorylation by protein phosphatase-III

Abstract

It has been established that glycogen synthetase activity in skeletal muscle can be regulated by two distinct protein kinases. One of these is cyclic AMPdependent protein kinase, while the other is an enzyme termed glycogen synthetase kinase-2 [ 1,2] . The phosphorylation of glycogen synthetase a in vitro by either kinase in the presence of ATP-Mg was found to reach a plateau when about one molecule of phosphate had been incorporated per subunit, and the resulting enzyme species were more dependent on the allosteric activator glucose-6-phosphate for activity. However cyclic AMP dependent protein kinase and glycogen synthetase kinase-2 produced different forms of glycogen synthetase, termed bi and bz respectively. These forms had different activity ratios (defined as the activity in the-absence of glucose-6-phosphate relative to the activity in the presence of this effector) and different activation constants (K,) for glucosedphosphate [2] . Moreover, the addition of both protein kinases resulted in the incorporation of almost two molecules of phosphate per subunit and the conversion of glycogen synthetase to a form, termed bl,2, which was almost completely inactive in the absence of glucosed-phosphate [2] . These results indicated that