Regulation of glycogen synthase activity by growth factors. Relationship between synthase activation and receptor occupancy.
Platelet-derived growth factor (PDGF) was found to stimulate the activity of glycogen synthase, an enzyme subjected to regulation by phosphorylation-dephosphorylation reactions. In Swiss mouse 3T3 cells, the time course of enzyme activation by PDGF is very similar to that of epidermal growth factor (EGF) and insulin. A 3-fold maximal stimulation was observed by 30 min, and the enzyme activity ratio returned to basal levels by 100 min. The PDGF effect was maximal at 1 ng/ml (30 pM) and half-maximal stimulation was observed at 0.2 ng/ml (6 pM). Parallel measurements of 125I-PDGF binding indicate that binding was maximal by 10 min and thus should not be rate-limiting for enzyme activation. In addition, presaturation of the receptors with PDGF at 4 degrees C did not expedite subsequent enzyme activation at 37 degrees C. Removal of PDGF in the media after the 4 degrees C pretreatment did not affect the enzyme activation response, indicating that the continued presence of PDGF in the medium is not necessary after receptor binding is saturated. Results of sequential addition of PDGF, EGF, and insulin indicated a refractory period in the response system. This property is evident even when the second addition involved a different growth factor and is independent of the sequence of addition of the factors. There was little additivity in the actions of the three growth factors in effecting enzyme activation and suggests a common intermediate element in the three signalling pathways.
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor
D006133:Growth Substances; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D006006:Glycogen Synthase; D017479:Receptors, Platelet-Derived Growth Factor