scholarly journals The inhibitory effect of phosphorylase a on the activation of glycogen synthase depends on the type of synthase phosphatase

1983 ◽  
Vol 212 (2) ◽  
pp. 407-416 ◽  
Author(s):  
L Mvumbi ◽  
F Doperé ◽  
W Stalmans
Keyword(s):  
Skeletal Muscle ◽  
Phosphatase Activity ◽  
Protein Kinases ◽  
Rat Liver ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Liver Extract ◽  
Inhibitory Effect ◽  
Specific Inhibition ◽  
Muscle Extract

The activity of glycogen synthase phosphatase in rat liver stems from the co-operation of two proteins, a cytosolic S-component and a glycogen-bound G-component. It is shown that both components possess synthase phosphatase activity. The G-component was partially purified from the enzyme-glycogen complex. Dissociative treatments, which increase the activity of phosphorylase phosphatase manyfold, substantially decrease the synthase phosphatase activity of the purified G-component. The specific inhibition of glycogen synthase phosphatase by phosphorylase a, originally observed in crude liver extracts, was investigated with purified liver synthase b and purified phosphorylase a. Synthase phosphatase is strongly inhibited, whether present in a dilute liver extract, in an isolated enzyme-glycogen complex, or as G-component purified therefrom. In contrast, the cytosolic S-component is insensitive to phosphorylase a. The activation of glycogen synthase in crude extracts of skeletal muscle is not affected by phosphorylase a from muscle or liver. Consequently we have studied the dephosphorylation of purified muscle glycogen synthase, previously phosphorylated with any of three protein kinases. Phosphorylase a strongly inhibits the dephosphorylation by the hepatic G-component, but not by the hepatic S-component or by a muscle extract. These observations show that the inhibitory effect of phosphorylase a on the activation of glycogen synthase depends on the type of synthase phosphatase.

scholarly journals Dephosphorylation and activation of exogenous glycogen synthase by adipose-tissue phosphatase

1980 ◽  
Vol 188 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Joan Heller Brown ◽  
Ronald D. Eichner ◽  
Barbara Thompson ◽  
Steven Mayer
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Protein Kinase ◽  
Phosphatase Activity ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Enzyme Activation ◽  
Phosphoprotein Phosphatase ◽  
Tissue Extracts ◽  
Lag Period

Exogenous purified rabbit skeletal-muscle glycogen synthase was used as a substrate for adipose-tissue phosphoprotein phosphatase from fed and starved rats in order to (1) compare the relationship between phosphate released from, and the kinetic changes imparted to, the substrate and (2) ascertain if decreases in adipose-tissue phosphatase activity account for the apparent decreased activation of endogenous glycogen synthase from starved as compared with fed rats. Muscle glycogen synthase was phosphorylated with [γ-32P]ATP and cyclic AMP-dependent protein kinase alone, or in combination with a cyclic AMP-independent protein kinase, to 1.7 or 3mol of phosphate per subunit. Adipose-tissue phosphatase activity determined with phosphorylated skeletal-muscle glycogen synthase as substrate was decreased by 35–60% as a consequence of starvation. This decrease in phosphatase activity had little effect on the capacity of adipose-tissue extracts to activate exogenous glycogen synthase (i.e. to increase the glucose 6-phosphate-independent enzyme activity), although there were marked differences in the activation profiles for the two exogenous substrates. Glycogen synthase phosphorylated to 1.7mol of phosphate per subunit was activated rapidly by adipose-tissue extracts from either fed or starved rats, and activation paralleled enzyme dephosphorylation. Glycogen synthase phosphorylated to 3mol of phosphate per subunit was activated more slowly and after a lag period, since release of the first mol of phosphate did not increase the glucose 6-phosphate-independent activity of the enzyme. These patterns of enzyme activation were similar to those observed for the endogenous adipose-tissue glycogen synthase(s): the glucose 6-phosphate-independent activity of the endogenous enzyme from fed rats increased rapidly during incubation, whereas that of starved rats, like that of the more highly phosphorylated muscle enzyme, increased only very slowly after a lag period. The observations made here suggest that (1) changes in glucose 6-phosphate-independent glycogen synthase activity are at best only a qualitative measure of phosphoprotein phosphatase activity and (2) the decrease in glycogen synthase phosphatase activity during starvation is not sufficient to explain the differential glycogen synthase activation in adipose tissue from fed and starved rats. However, alterations in the phosphorylation state of glycogen synthase combined with decreased activity of phosphoprotein phosphatase, both as a consequence of starvation, could explain the apparent markedly decreased enzyme activation.

Effects of insulin treatment on the activities of phosphoprotein phosphatase and its inhibitors

1980 ◽  
Vol 95 (3) ◽  
pp. 427-432 ◽  
Author(s):  
L. Y. Chang ◽  
L. C. Huang
Keyword(s):  
Skeletal Muscle ◽  
Phosphatase Activity ◽  
Glycogen Synthase ◽  
Rat Skeletal Muscle ◽  
Phosphoprotein Phosphatase ◽  
Heat Stable ◽  
Muscle Extract ◽  
Wide Range ◽  
Heat Stable Protein

Abstract. An increase in glycogen synthase phosphatase (phosphoprotein phosphatase) activity was observed in the rat skeletal muscle extract following insulin administration. The phosphoprotein phosphatase activity present in the muscle extract from insulin treated rats was observed to remain elevated after the extract had been subjected to a molecular sieve chromatography. These results indicate that the stimulatory effets of insulin is due to modification of phosphatase itself or some macromolecular weight modifiers. The heat-stable protein inhibitors of the phosphoprotein phosphatase were isolated from skeletal muscle of insulin treated and control rats and their inhibitory potencies were compared over a wide range of protein concentrations. The inhibitory potency in the insulin treated rat skeletal muscle was found to be significantly less than that in the control muscle. Since type-1 inhibitor is well-known to be active only after being phosphorylated by cyclic AMP-dependent protein kinase, we suggest that the observed change in phosphoprotein phosphatase inhibitor potency is most likely mediated by an alteration in the phosphorylation state of type-1 inhibitor.

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