Interleukin-17 receptor
Interleukin-17 receptor (IL-17R) is a cytokine receptor which binds interleukin 17A.[2] Functional IL-17R is a heteromeric complex consisting of at least IL17RA and IL17RC.[3]
A number of additional variants exist including IL17RB,[4] which binds preferentially IL17B and IL17E.[5][6] A total of five members of the family have been identified.[7] The first identified member, IL-17RA is located on human chromosome 22.
Evolution
There are two IL17Rs (IL17RA and IL17RD) in the genome of the basal chordate Amphioxus.[8] After two rounds of whole genome duplications, these two IL17R genes expanded into five early vertebrate IL17R genes, IL17RA to IL17RE. Two (IL17RA and IL17RD) are found in most vertebrates, whereas the other three (IL17RB, ILR17RC and IL17RE) have undergone some losses in vertebrates during evolution.
Structure
IL-17A and IL-17RA are founding members of a new subfamily receptors A-F. IL-17RA is by far the largest member of the family and has the largest cytoplasmic tail of the family. This cytoplasmic tail provides docking sites for numerous signaling intermediates. IL-17RA is composed of both alpha helices and beta sheets and has fibronectin domains, beta-sandwich domains, and ectodomains.[9]
Clinical significance
IL-17A neutralizing antibodies have the potential for the treatment of autoimmune diseases in humans. It also may soon be used for protection against periodontal bone loss as it is currently being tested in mice. IL-17 RA has been observed at high levels in people undergoing treatment for cardiac fibroblasts and in certain tissues such as: haematopoietic, bone marrow, thymus, and spleen tissue. IL-17 RA is also normally found in low levels in colon, small intestine, and lung tissues.[10]
See also
References
- ↑ PDB: 3JVF; Ely LK, Fischer S, Garcia KC (December 2009). "Structural basis of receptor sharing by interleukin 17 cytokines". Nat. Immunol. 10 (12): 1245–51. doi:10.1038/ni.1813. PMC 2783927. PMID 19838198.
- ↑ Yao Z, Spriggs MK, Derry JM, Strockbine L, Park LS, VandenBos T, Zappone JD, Painter SL, Armitage RJ (1997). "Molecular characterization of the human interleukin (IL)-17 receptor". Cytokine 9 (11): 794–800. doi:10.1006/cyto.1997.0240. PMID 9367539.
- ↑ Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006). "Cutting edge: interleukin 17 signals through a heteromeric receptor complex". J. Immunol. 177 (1): 36–9. doi:10.4049/jimmunol.177.1.36. PMID 16785495.
- ↑ Tian E, Sawyer JR, Largaespada DA, Jenkins NA, Copeland NG, Shaughnessy JD (2000). "Evi27 encodes a novel membrane protein with homology to the IL17 receptor". Oncogene 19 (17): 2098–109. doi:10.1038/sj.onc.1203577. PMID 10815801.
- ↑ Shi Y, Ullrich SJ, Zhang J, Connolly K, Grzegorzewski KJ, Barber MC, Wang W, Wathen K, Hodge V, Fisher CL, Olsen H, Ruben SM, Knyazev I, Cho YH, Kao V, Wilkinson KA, Carrell JA, Ebner R (2000). "A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity". J. Biol. Chem. 275 (25): 19167–76. doi:10.1074/jbc.M910228199. PMID 10749887.
- ↑ Lee J, Ho WH, Maruoka M, Corpuz RT, Baldwin DT, Foster JS, Goddard AD, Yansura DG, Vandlen RL, Wood WI, Gurney AL (2001). "IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1". J. Biol. Chem. 276 (2): 1660–4. doi:10.1074/jbc.M008289200. PMID 11058597.
- ↑ Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K (February 2009). "Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin". Br. J. Dermatol. 160 (2): 319–24. doi:10.1111/j.1365-2133.2008.08902.x. PMID 19016708.
- ↑ Wu B, Jin M, Zhang Y, Wei T, Bai Z (July 2011). "Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL". Immunogenetics 63 (12): 835–45. doi:10.1007/s00251-011-0554-4. PMID 21732179.
- ↑ Gaffen SL (August 2009). "Structure and signalling in the IL-17 receptor family". Nat. Rev. Immunol. 9 (8): 556–67. doi:10.1038/nri2586. PMC 2821718. PMID 19575028.
- ↑ Ho AW, Gaffen SL (March 2010). "IL-17RC: a partner in IL-17 signaling and beyond". Semin Immunopathol 32 (1): 33–42. doi:10.1007/s00281-009-0185-0. PMC 2837117. PMID 20012905.
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