Formulation: Lyophilized from sterile PBS, pH 7.4
Purity: ≥95% estimated by SDS-PAGE
Shelf life (days): 365
Notes: Receptor activator of NF-κB ligand (RANKL), also known as osteoclast differentiation factor (ODF), is a type II transmembrane protein and member of the TNF cytokine family that has roles in bone remodeling, osteoclast differentiation, and immune cell regulation.{67556,67557,67558} It is composed of a cytoplasmic domain, a transmembrane domain, and an extracellular binding domain.{67556,67557,67558} RANKL is widely expressed but is highly expressed in precursor osteoclasts and maturing lymphocytes.{42925,67561,67560} It binds as a soluble homotrimer to its receptor, RANK, to induce signaling via the NF-κB, JNK, ERK, p38, nuclear factor of activated T cells (NFAT), and Akt pathways.{42924,60909,67556} RANKL also binds to osteoprotegrin (OPG), which prevents RANKL from activating RANK signaling.{67559} TNFSF11, the gene encoding RANKL, is differentially transcribed to produce three isoforms: RANKL 1 and RANKL 2, which contain all three domains, and RANKL 3, which contains only the extracellular domain.{67558} The extracellular domain can also be cleaved from full-length RANKL by the proteases disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) or matrix metalloproteinases-7 (MMP-7) to produce soluble RANKL extracellular domain.{67560} RANKL 1 promotes osteoclastogenesis while RANKL 3 decreases the ratio of osteoclasts to preosteoclasts. Recombinant RANKL extracellular domain induces dendritic cell aggregation and clustering and increases dendritic cell activation.{67557} Serum levels of the RANKL extracellular domain are elevated in patients with multiple myeloma and are negatively correlated with prognosis.{67561} Cayman’s RANKL/ODF Extracellular Domain (human, recombinant) protein can be used for binding and cellular activity assay applications. This protein is a disulfide-linked homodimer. The reduced monomer, composed of RANKL/ODF Extracellular Domain (amino acids 64-245) fused to rabbit IgG Fc at its N-terminus, consists of 181 amino acids and has a calculated molecular weight of 134.21 kDa. As a result of glycosylation, the monomer migrates at approximately 45-55 kDa by SDS-PAGE under reducing conditions.
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