CHARACTERIZATION OF PLATELET-DERIVED GROWTH-FACTOR-ALPHA RECEPTOR SYNTHESIS AND METABOLIC TURNOVER

Cellular responses to the AA isoform of platelet-derived growth factor (PDCF-AA) are mediated via the PDGF alpha receptor. Several studies s uggest this receptor may signal pathways distinct from those activated by the PDCF beta receptor. Because alpha receptors are less well char acterized than are beta receptors, and because the quantity of cell su rface PDGF receptors governs the extent and perhaps type of PDGF-stimu lated response, we examined the synthesis and degradation of alpha rec eptors 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 rece ptor turnover, pretreatment of cells with PDGF-AA and essentially comp lete down-regulation of alpha receptors did not correspondingly increa se the level of alpha receptor synthesis. These findings indicate that the number of cell surface PDGF alpha receptors is regulated by the r ate of internalization of these receptors. Lastly, we report that the recovery of PDGF-AA binding following down-regulation of alpha recepto rs is not affected by inhibition of RNA synthesis. Thus, repopulation of cell surface PDCF alpha receptors may not necessitate an increase i n the level of PDCF alpha receptor mRNA.