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Overexpression of IL\u20106 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post\u2010menopausal osteoporosis. Hence, selective antagonists of IL\u20106 action may offer therapeutic benefits. IL\u20106 is a member of the family of cytokines that includes interleukin\u201011, leukemia inhibitory factor, oncostatin M, cardiotrophin\u20101, and ciliary neurotrophic factor. Like the other members of this family, IL\u20106 induces growth or differentiation via a receptor\u2010system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL\u20106 that are involved in the interactions with the IL\u20106 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL\u20106 which interact with its low\u2010affinity specific receptor, the IL\u20106 receptor, and the high\u2010affinity converter gp130. A tentative model for the IL\u20106 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL\u20106 family of cytokines.<\/jats:p>","DOI":"10.1002\/pro.5560060501","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T05:49:18Z","timestamp":1234244958000},"page":"929-955","source":"Crossref","is-referenced-by-count":306,"title":["Interleukin\u20106: Structure\u2010function relationships"],"prefix":"10.1002","volume":"6","author":[{"given":"Richard J.","family":"Simpson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet","family":"Hammacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry D.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.18.6434"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60532-5"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1993.39"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)81033-5"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1991.tb16048.x"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/380041a0"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114392"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"19853","DOI":"10.1016\/S0021-9258(17)45451-2","article-title":"Molecular cloning, characterization and functional expression of the rat liver interleukin 6 receptor","volume":"265","author":"Baumann M","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8374"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.1.138"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4049\/jimmunol.157.1.284","article-title":"Complex of the soluble IL\u201011 receptor and IL\u201011 acts as IL\u20106 type cytokine in hepatic and nonhepatic cells","volume":"157","author":"Baumann H","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91528-3"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90139-Z"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.6934"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90182-E"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90258-2"},{"key":"e_1_2_1_18_1","first-page":"279","article-title":"Aleutian mink disease: Puzzles and paradigms","volume":"3","author":"Bloom ME","year":"1994","journal-title":"Infectious agents and disease"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(84)71582-8"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-9822(93)90002-6"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"11648","DOI":"10.1016\/S0021-9258(19)78174-5","article-title":"Ciliary neurotrophic factor\/leukemia inhibitory factor\/interleukin 6\/oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors","volume":"269","author":"Boulton TG","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-204-43666"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.139.12.4116"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42317-9"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.4049\/jimmunol.143.4.1175","article-title":"Analysis of human interleukin\u20106 mutants expressed in E. coli: Biological activities are not affected by deletion of amino acids 1\u201328","volume":"743","author":"Brakenhoff JPJ","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.4049\/jimmunol.145.2.561","article-title":"Structurefunction analysis of human IL\u20106. 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