The low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor is a receptor for connective tissue growth factor

Connective tissue growth factor (CTGF) expression is regulated by transform ing growth factor-beta (TGF-beta) and strong up-regulation occurs during wo und healing; in situ hybridization data indicate that there are high levels of CTGF expression in fibrotic lesions. Recently the binding parameters of CTGF to both high and lower affinity cell surface binding components have been characterized. Affinity cross-linking and SDS-polyacrylamide gel elect rophoresis analysis demonstrated the binding of CTGF to a cell surface prot ein with a mass of similar to 620 kDa. We report here the purification of t his protein by affinity chromatography on CTGF coupled to Sepharose and seq uence information obtained by mass spectroscopy. The binding protein was id entified as the multiligand receptor, low density lipoprotein receptor-rela ted protein/alpha (2)-macroglobulin receptor (LRP). The identification of L RP as a receptor for CTGF was validated by several studies: 1) binding comp etition with many ligands that bind to LRP, including receptor-associated p rotein; 2) immunoprecipitation of CTGF-receptor complex with LRP antibodies ; and 3) cells that are genetically deficient for LRP were unable to bind C TGF. Last, CTGF is rapidly internalized and degraded and this process is LR P-dependent. In summary, our data indicate that LRP is a receptor for CTGF, and may play an important role in mediating CTGF biology.