Very low density lipoprotein receptor from mammary gland and mammary epithelial cell lines binds and mediates endocytosis of Mr, 40,000 receptor associated protein

Abstract

We here report that the M _r 40,000 receptor associated protein (RAP), previously found to bind to α₂-macroglobulin receptor/low density lipoprotein receptor related protein (α₂MR/LRP) and glycoprotein 330 (gp330), binds to an M _r, 105,000 membrane protein from bovine mammary gland, human mamma tumors and mammary epithelial cell lines. We have purified this protein from bovine and human sources. N-terminal amino acid sequencing and immunoblotting analyses showed that the protein was identical or closely related to very low density lipoprotein receptor (VLDL-R). Experiments with the human mamma carcinoma cell line MCF-7 showed that this receptor was able to mediate an efficient endocytosis of RAP. These novel findings strongly suggest that RAP functions as a modulator of ligand binding to VLDL-R, similarly to α₂MR/LRP and gp330.