Recombinant Human Lgr5/GPR49 Fc Chimera Protein, CF

Lgr5 (leucine-rich repeat G-protein coupled receptor 5), also called GPR49, is a seven-transmembrane glycoprotein receptor in the Lgr family of cell surface receptors (1, 2). While this family includes receptors for hormones such as LH, FSH, TSH, and HCG, the subfamily comprising Lgr4, Lgr5, and Lgr6 are G-protein independent mediators of the potentiating effect of R-Spondins on Wnt signaling (1-6). Lgr5 binds and forms complexes with R-Spondins, Frizzled Wnt receptors and LRP Wnt coreceptors (3-5). It acts at least in part by enhancing Wnt-dependent LRP phosphorylation, internalization of LRPs, and accumulation of beta-catenin (3-5). Human Lgr5 cDNA encodes 907 amino acids (aa), including a long N-terminal extracellular domain (ECD, aa 22-561) with 16-17 LRR domains that mediate ligand interaction (2). The LRR-containing ECD of human Lgr5 shares 90% aa sequence identity with mouse and rat Lgr4, and 50-60% aa identity with human Lgr4 and Lgr6. Lgr5 is expressed by embryonic and adult epithelial stem cells, especially in the intestines, stomach, hair follicles, inner ear and mammary glands (1, 5, 6). Lgr4 is also present in epithelial stem cells, but shows wider expression elsewhere, making Lgr5 the preferred marker for these cells (5). Lgr5⁺ stem cells are sufficient to produce all epithelial cell types of the intestinal crypts in vivo or in vitro, when supported by secreted factors from neighboring Paneth or goblet cells (1, 7). In the embryo, Lgr5 is involved in development of the kidney and craniofacial structures (1). It is up-regulated in stem cells that give rise to cancers such as intestinal, hepatocellular, pancreatic and ovarian carcinomas, and may promote carcinogenesis (6).