RANKL, aa85-245, Recombinant, Human (Receptor Activator of Nuclear Factor kappa B Ligand, Receptor Activator of NFkB Ligand, CD254, hRANKL2, hRANKL-2, Osteoclast Differentiation Factor, ODF, Osteoprotegerin Ligand, OPGL, sOdf, SOFA, TNF-related Activation

RANK L, is a 39-45kD 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 317aa, including a 47aa cytoplasmic domain, a 21aa TM region, and a 249aa extracellular domain (ECD) with two potential N-linked glycosylation sites (note: aa85-245 of Accession # AAC51762 is identical to aa157-317 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 24kD forms of RANK L can be created by usage of alternate start sites at aa74 or 146, or proteolytic cleavage by osteoblast- or stromal cell-derived ADAM10 (after aa139) or MMP14 (146aa), or bone metastatic prostate tumor-derived MT1-MMP (aa146) (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).\n\nSource: \nRecombinant corresponding to aa85-245 from human RANK L with an N-terminal Met expressed in E. coli.\n\nMolecular Weight: \n~18.3kD\n\nEndotoxin Level: \n(same/less than)1EU/1ug (LAL)\n\nBiological Activity:\nMeasured by its ability to induce osteoclast differentiation on RAW 264.7 mouse macrophages.\nThe ED50 for this effect is typically 2-12ng/mL\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with PBS. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 6 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

R1075-10U

Size

10ug

Form

Supplied as a lyophilized powder in sodium dihydrogen phosphate, sodium chloride, EDTA. Reconstitute with PBS to 100ug/ml.

Purity

~90% (SDS-PAGE)

References

1. Leibbrandt, A. and J.M. Penninger 2008) Ann. N. Y. Acad. Sci. 1143:123. 2. Wong, B.R. et al. (1997) J. Biol. Chem. 272:25190. 3. Anderson, D.M. et al. (1997) Nature 390:175. 4. Lacey, D.L. et al. (1998) Cell 93:165. 5. Hikita, A. et al. (2006) J. Biol. Chem. 281:36846. 6. Kong, Y-Y. et al. (1999) Nature 397:315. 7. Accession #NP_143026 and EAX08679. 8. Sabbota, A.L. et al. (2010) Cancer Res. 70:5558. 9. Aoki, S. et al. (2010) J. Bone Miner. Res. 25:1907. 10. Fata, J.E. et al. (2000) Cell 103:41. 11. Hanada, R. et al. (2009) Nature 426:505. 12. Osako, M.K. et al. (2010) Circ. Res. 107:466. 13. Schramek, D. et al. (2010) Nature 468:98. 14. Gonzalez-Suarez, E. et al. (2010) Nature 468:103. 15. Dougall, W.C. and M. Chaisson (2006) Cancer Metastasis Rev. 25:541. 16. Sobacchi, C. et al. (2007) Nat. Genet. 39:960.