Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation.
Platelet-derived growth factor (PDGF) has previously been shown to bind to a specific high affinity receptor on human foreskin fibroblasts. The present study was carried out to characterize some of the cellular events resulting from the interaction of the ligand with its receptor. Radiolabeled PDGF was rapidly internalized and degraded after binding to the cells. The degradation was complete and was inhibited by low concentrations of the lysosomotropic agents, chloroquine, ammonium chloride, or methylamine, suggesting that the degradation occurs in the lysosomes. The cellular binding capacity for PDGF decreased after exposure of the cells to PDGF at 37 degrees C. This down regulation of the PDGF receptor was optimal after a 60-min incubation at 37 degrees C and half-maximal at 0.5 nM concentration of PDGF. The binding capacity was restored when the PDGF-containing medium was changed to medium without PDGF; the binding capacity increased from 40 to 80% od the initial value after a 4-h incubation at 37 degrees C. The reappearance on the cell surface of PDGF-binding sites was dependent on protein synthesis and totally blocked by cycloheximide (20 micrograms/ml). Thus, either the receptor has to be resynthesized after internalization or, alternatively, any step in the recycling of "used" receptors is dependent on protein synthesis. Exposure of the cells to PDGF also caused a dose-dependent decrease in the binding capacity for epidermal growth factor which has a distinct receptor on these cells. In contrast, epidermal growth factor did not modulate the PDGF binding capacity, lending no support to the idea that the receptors for epidermal growth factor and PDGF are processed in a common pathway.
D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D012867:Skin / Q000378:metabolism
D006133:Growth Substances; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor