Epidermal growth factor stimulates glycogen synthase activity in cultured cells.

Addition of epidermal growth factor (EGF) to quiescent cultured cells was found to stimulate the activity of glycogen synthase (UDPglucose:glycogen 4-alpha-D-glucosyltransferase, EC 2.4.1.11), an enzyme subjected to regulation by covalent modification. In Swiss mouse 3T3 cells, the activation by EGF paralleled the effect seen with insulin; the time course and dose-response curves of the two polypeptide factors were similar. Stimulation of enzyme activity ratio [(activity in the absence of glucose 6-phosphate)/(activity in the presence of glucose 6-phosphate)] was maximal after 20-30 min of incubation. Both factors caused a maximal stimulation of 2.5-fold in synthase activity ratio at approximately equal to 10 nM, and the half-maximal effect was observed at 0.1-1 nM. Insulin and EGF exhibited partial additivity in effecting this enzyme activation. In contrast, human A431 cells showed no response to insulin. Although quantitatively different, the EGF effect in the latter cells was time dependent, reaching a maximum at 90 min, and dose dependent, with a maximal stimulation of 4-fold in synthase activity ratio at 10 nM. Half-maximal effect was observed at 0.3 nM EGF. Direct quantitation of allosteric effectors (glucose 6-phosphate, adenine nucleotides, and Pi) present in the enzyme assay mixtures indicated that the observed activation was not simply a consequence of changes in metabolite concentrations. These results suggest that EGF may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms.