Recombinant Human TRANCE/RANK L/TNFSF11 (E. coli-expressed)

RANK L (receptor activator of NF-kappa B ligand), also called TRANCE (TNF-related activation-induced cytokines), OPGL (osteoprotegerin ligand), or ODF (osteoclast differentiation factor), is a 39‑45 kDa type II transmembrane (TM) protein in the tumor necrosis factor family, designated TNFSF11 (1‑5). RANK L, produced by osteoblasts and bone marrow stromal cells, is required for differentiation of osteoclasts and stimulates bone resorption (4, 6). It is also produced by activated T cells and augments dendritic cell stimulation; RANK L^-/- mice lack lymph nodes and have impaired thymocyte development (1‑3, 6). The human RANK L cDNA encodes 317 amino acids (aa), including a 47 aa cytoplasmic domain, a 21 aa TM region, and a 249 aa extracellular domain (ECD) with two potential N‑linked glycosylation sites (note: Arg85‑Asp245 of Accession # AAC51762 is identical to Arg157‑Asp317 of SwissProt # O14788. This aa range contains the ECD trimerization and receptor‑binding motifs, but not ECD proteolytic cleavage sites). Within the ECD, human RANK L shares 89%, 89%, 93% and 95% aa identity with mouse, rat, bovine and porcine RANK L, respectively. Mouse RANK L can stimulate human osteoclast differentiation (4). Like most TNF family members, RANK L can form trimers (1). Soluble 31, 25 and 24 kDa forms of RANK L can be created by usage of alternate start sites at aa 74 or 146, or proteolytic cleavage by osteoblast- or stromal cell‑derived ADAM10 (after aa 139) or MMP14 (aa 146), or bone metastatic prostate tumor-derived MT1-MMP (aa 146) (5, 7, 8). Both TM and soluble extracellular RANK L act by engaging RANK receptors and are antagonized by the decoy receptor, OPG (osteoprotegrin) (2, 5). In resting cells, the majority of RANK L is stored in secretory lysosomes (9). In mammary epithelia, RANK L is upregulated by pregnancy hormones and is essential for the formation of a lactating mammary gland (10). In the brain, astrocyte RANK L mediates body temperature regulation (11). Pathologically, RANK L is thought to mediate post-menopausal osteoporosis, vascular calcification, progestin-induced breast cancer, cancer-induced bone disease, and osteopetrosis (in RANK L deficiencies) (12‑16).