MOLECULAR-CLONING AND CHARACTERIZATION OF LR3, A NOVEL LDL RECEPTOR FAMILY PROTEIN WITH MITOGENIC ACTIVITY

We report molecular cloning and initial functional characterization of a novel member of the low density lipoprotein receptor (LDLR) gene fa mily. The cDNA was isolated from a human osteoblast cDNA library and e ncoded a 1,615 amino acids protein designated as LR3. It has, in the e xtracellular region, a cluster of three LDLR ligand binding repeats at a juxtamembrane position and four EGF precursor homology domains sepa rated by YWTD spacer repeats. The entire ectodomain shares the same mo dular organization with the middle portion of the extracellular region s of two LDLR family members, LDLR-related protein (LRP), and gp330/me galin. LR3 mRNA was expressed in most of the adult and fetal tissues e xamined. The highest expression level was seen in aorta. In human oste osarcoma cells examined, LR3 mRNA was highly enriched in TE85 cells, m oderately expressed in MG63 cells and primary human osteoblasts, and u ndetectable in SaOS-2 cells. NIH 3T3 cells transfected with either ful l length LR3 or its ectodomain showed significantly increased prolifer ation, whereas transfection of intracellular domain had no proliferati ve effect. We predict that LR3 is a multi-functional protein with pote ntial mitogenic activity. (C) 1998 Academic Press.