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

✍ Scribed by Lihua Wu; Sanja Arandjelovic; Steven L. Gonias

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 216 KB
• Volume: 93
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20288

✦ Synopsis

Abstract

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 β‐receptor or PDGF β‐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 β‐receptor. In MEFs, the mechanism involved increased PDGF β‐receptor transcription and/or RNA stabilization. LRP‐1 expression was not associated with increased levels of PDGF β‐receptor in Chinese hamster ovary (CHO) cells, suggesting that cell context is important. The kinetics of PDGF β‐receptor phosphorylation, in response to PDGF‐BB, and the extent of degradation of PDGF β‐receptor were equivalent in LRP‐1‐expressing and ‐deficient MEFs. We conclude that PDGF β‐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 β‐receptor phosphorylation or degradation in PDGF‐BB‐treated cells. © 2004 Wiley‐Liss, Inc.