|Detection of Lgr4/GPR48 in HEK293 Human Cell Line Transfected with Human Lgr4/GPR48 and eGFP by Flow Cytometry. HEK293 human embryonic kidney cell line transfected with human Lgr4/GPR48 and eGFP was stained with either (A) Mouse Anti-Human Lgr4/GPR48 APC‑conjugated Monoclonal Antibody (Catalog # FAB7750A) or (B) Mouse IgG2B Allophycocyanin Isotype Control (Catalog # IC0041A). View our protocol for Staining Membrane-associated Proteins.|
Lgr4 (Leucine-rich repeat GPR 4), also known as GPR48 (G-Protein-coupled Receptor 48), 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). Lgr4 binds and forms complexes with R-Spondins, Frizzled Wnt receptors, and LRP Wnt co-receptors (5). It acts, at least in part, by enhancing Wnt-dependent LRP phosphorylation, internalization of LRPs, and accumulation of beta -catenin (3, 4). Human Lgr4 cDNA encodes 951 amino acids (aa), including a long N-terminal Extracellular Domain (ECD, aa 25-544) with 16-17 LRR domains that mediate ligand interaction (1). The LRR-containing ECD of human Lgr4 shares 93% aa sequence identity with mouse, rat and bovine Lgr4, and 50-60% aa identity with human Lgr5 and Lgr6. Lgr4 is widely expressed in both embryo and adult. Expression of Lgr4 mRNA in adult humans is highest in pancreas, followed by liver, heart, muscle, brain, and placenta (1). In rodents, embryonic and adult expression includes liver, kidney, adrenals, bone/cartilage, and heart (2, 7-9). Lgr4 deletion in the mouse affects development in areas of normal expression, for example, it will inhibit fetal liver definitive erythropoiesis (9). Deletion of Lgr4 specifically from stem and progenitor cells in intestinal crypts induces loss of crypts due to insufficient Wnt signaling (5, 6). Lgr4 may be over-expressed in carcinomas and may promote invasiveness and metastasis by down-regulating p27Kip1 expression (10).