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 family. The cDNA was isolated from a human osteoblast cDNA library and encoded a 1,615 amino acids protein designated as LR3. It has, in the extracellular region, a cluster of three LDLR ligand binding repeats at a juxtamembrane position and four EGF precursor homology domains separated by YWTD spacer repeats. The entire ectodomain shares the same modular organization with the middle portion of the extracellular regions of two LDLR family members, LDLR-related protein (LRP), and gp330/megalin. LR3 mRNA was expressed in most of the adult and fetal tissues examined. The highest expression level was seen in aorta. In human osteosarcoma cells examined, LR3 mRNA was highly enriched in TE85 cells, moderately expressed in MG63 cells and primary human osteoblasts, and undetectable in SaOS-2 cells. NIH 3T3 cells transfected with either full length LR3 or its ectodomain showed significantly increased proliferation, whereas transfection of intracellular domain had no proliferative effect. We predict that LR3 is a multi-functional protein with potential mitogenic activity.
Dong
Y
Y
Pharmaceutical Division, Bayer Corporation, West Haven, Connecticut, 06516-4175, USA.
Lathrop
W
W
Weaver
D
D
Qiu
Q
Q
Cini
J
J
Bertolini
D
D
Chen
D
D
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004815:Epidermal Growth Factor / Q000235:genetics; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008934:Mitogens / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010006:Osteoblasts / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics*; D011994:Recombinant Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D026541:Heymann Nephritis Antigenic Complex; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D008562:Membrane Glycoproteins; D008934:Mitogens; D011973:Receptors, LDL; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor