Effects of low density lipoprotein receptor-related protein-1 on the expression of platelet-derived growth factor beta-receptor in vitro.
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.
Wu
Lihua
L
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Arandjelovic
Sanja
S
Gonias
Steven L
SL
D000818:Animals; D000077214:Becaplermin; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D005354:Fibrosarcoma; D006579:Heterozygote; D056488:Histone Chaperones; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; C466234:UIMC1 protein, human; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta