Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. Osteoprotegerin (OPG) is a decoy receptor for RANKL, and regulates the stimulation of the RANK signaling pathway by competing for RANKL. The cytoplasmic domain of RANK binds TRAFs 1, 2, 3, 5, and 6 which transmit signals to downstream targets such as NF-κB and JNK.
RANK is constitutively expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cell,[5] and pancreas. Most commonly, activation of NF-κB is mediated by RANKL, but over-expression of RANK alone is sufficient to activate the NF-κB pathway.[6]
RANKL (receptor activator for nuclear factor κ B ligand) is found on the surface of stromal cells, osteoblasts, and T cells.[7][8][9] Mutations affecting RANK have been associated with infantile malignant osteopetrosis in humans, mice and cats.[10]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000141655 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026321 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Sattler AM, Schoppet M, Schaefer JR, Hofbauer LC (2004). "Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and vascular disease". Calcif. Tissue Int. 74 (1): 103–106. doi:10.1007/s00223-003-0011-y. PMID 14523602. S2CID 10628044.
- ^ Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L (1997). "A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function". Nature. 390 (6656): 175–179. Bibcode:1997Natur.390..175A. doi:10.1038/36593. PMID 9367155. S2CID 4373990.
- ^ Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999). "Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families". Endocr. Rev. 20 (3): 345–357. doi:10.1210/edrv.20.3.0367. PMID 10368775.
- ^ Wong BR, Josien R, Choi Y (1999). "TRANCE is a TNF family member that regulates dendritic cell and osteoclast function". J. Leukoc. Biol. 65 (6): 715–724. doi:10.1002/jlb.65.6.715. PMID 10380891. S2CID 17303204.
- ^ Theill LE, Boyle WJ, Penninger JM (2002). "RANK-L and RANK: T cells, bone loss, and mammalian evolution". Annu. Rev. Immunol. 20: 795–823. doi:10.1146/annurev.immunol.20.100301.064753. PMID 11861618.
- ^ Bridavsky M, Kuhl H, Woodruff A, Kornak U, Timmermann B, Mages N, 99 Lives Consortium, Lupiáñez DG, Symmons O, Ibrahim DM (22 February 2019). "Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly". bioRxiv 10.1101/556761. S2CID 91203744