Substrate specific activation by glucose 6-phosphate of the dephosphorylation of muscle glycogen synthase

The activation of glycogen synthase by insulin is in many instances stimulated by the presence of extracellular glucose. Previous observations in cell extracts, glycogen pellets and other crude systems suggest that this stimulation may be due to an increase in glucose 6-phosphate, which activates the dephosphorylation of glycogen synthase by protein phosphatases. Using purified rabbit muscle glycogen synthase D and protein phosphatases 1 and 2A, the types responsible for the activation of muscle synthase, it was found that glucose 6-phosphate, at low, physiological concentrations, stimulated the dephosphorylation of glycogen synthase. Both types of phosphatase were stimulated to the same extent when acting on glycogen synthase. The dephosphorylation of other protein substrates of the phosphatases was either not affected or inhibited by glucose 6-phosphate. It appears that the stimulatory effect of glucose 6-phosphate at physiological concentrations is apparently specific for glycogen synthase, and most likely due to an allosteric configuration change of this enzyme which facilitates its dephosphorylation. In addition, the effects of other reported modulators of glycogen synthase dephosphorylation, AMP, ATP and Mg2+, were studied in this 'in vitro' system.