Characterization of platelet-derived growth factor alpha receptor synthesis and metabolic turnover.
Cellular responses to the AA isoform of platelet-derived growth factor (PDGF-AA) are mediated via the PDGF alpha receptor. Several studies suggest this receptor may signal pathways distinct from those activated by the PDGF beta receptor. Because alpha receptors are less well characterized than are beta receptors, and because the quantity of cell surface PDGF receptors governs the extent and perhaps type of PDGF-stimulated response, we examined the synthesis and degradation of alpha receptors in BALB/c-3T3 cells. Our data show that the ligand-independent half-life of alpha receptors is 3 h and that optimal turnover of alpha receptors requires protein synthesis. In the presence of ligand, the half-life of alpha receptors markedly decreases and is independent of protein synthesis. Although PDGF-AA accelerated the rate of alpha receptor turnover, pretreatment of cells with PDGF-AA and essentially complete down-regulation of alpha receptors did not correspondingly increase the level of alpha receptor synthesis. These findings indicate that the number of cell surface PDGF alpha receptors is regulated by the rate of internalization of these receptors. Lastly, we report that the recovery of PDGF-AA binding following down-regulation of alpha receptors is not affected by inhibition of RNA synthesis. Thus, repopulation of cell surface PDGF alpha receptors may not necessitate an increase in the level of PDGF alpha receptor mRNA.
Coats
S R
SR
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615.
Olashaw
N E
NE
Pledger
W J
WJ
D016475:3T3 Cells; D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D006207:Half-Life; D008024:Ligands; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism*
D008024:Ligands; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor