Effects of low density lipoprotein receptor-related protein-1 on the expression of platelet-derived growth factor...

The low density lipoprotein receptor related protein-1 (LRP-1) is a cargo transport receptor that undergoes constitutive endocytosis and recycling. Platelet-derived growth factor-BB (PDGF-BB) binds to LRP-1 and may bridge LRP-1 to PDGF receptors. Bridging of LRP-1 to other receptors by bifunctional ligands may represent a general mechanism whereby LRP-1 facilitates internalization of membrane proteins. The goal of this study was to determine whether LRP-1 regulates cell-surface levels of PDGF beta-receptor or PDGF beta-receptor degradation following treatment with PDGF-BB. Unexpectedly, in both murine embryonic fibroblasts (MEFs) and HT 1080 fibrosarcoma cells, LRP-1 expression was associated with increased levels of PDGF beta-receptor. In MEFs, the mechanism involved increased PDGF beta-receptor transcription and/or RNA stabilization. LRP-1 expression was not associated with increased levels of PDGF beta-receptor in Chinese hamster ovary (CHO) cells, suggesting that cell context is important. The kinetics of PDGF beta-receptor phosphorylation, in response to PDGF-BB, and the extent of degradation of PDGF beta-receptor were equivalent in LRP-1-expressing and -deficient MEFs. We conclude that PDGF beta-receptor expression and cell surface levels may be regulated by LRP-1; however, this activity is cell type-specific. LRP-1 does not directly regulate PDGF beta-receptor phosphorylation or degradation in PDGF-BB-treated cells.