Interleukin-6 receptor explained

Interleukin 6 receptor (IL6R) also known as CD126 (Cluster of Differentiation 126) is a type I cytokine receptor.

Function

Interleukin 6 (IL6) is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in immune response. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer.

In melanocytes IL6R gene expression may be regulated by MITF.^[1]

Structure

The IL6 receptor is a protein complex consisting of an IL-6 receptor subunit (IL6R) and interleukin 6 signal transducer Glycoprotein 130. IL6R also denotes the human gene encoding this subunit. Alternatively spliced transcript variants encoding distinct isoforms have been reported.^[2] IL6R subunit is also shared by many other cytokines.

Interactions

Interleukin-6 receptor has been shown to interact with Interleukin 6^{[3] [4] [5]} and ciliary neurotrophic factor.^{[4] [6]}

See also

• Cluster of differentiation
• Anti-IL-6
  • Tocilizumab, a monoclonal antibody against IL6R
  • Sarilumab, a monoclonal antibody against IL6R

References

Further reading

• Krause E, Wegenka U, Möller C, Horn F, Heinrich PC . Gene expression of the high molecular weight proteinase inhibitor alpha 2-macroglobulin . Biol. Chem. Hoppe-Seyler . 373 . 7 . 509–15 . 1992 . 1381187 . 10.1515/bchm3.1992.373.2.509 .
• Schooltink H, Stoyan T, Roeb E, Heinrich PC, Rose-John S . Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes . FEBS Lett. . 314 . 3 . 280–4 . 1992 . 1281789 . 10.1016/0014-5793(92)81489-9 . 39538295 . free .
• Schooltink H, Stoyan T, Lenz D, Schmitz H, Hirano T, Kishimoto T, Heinrich PC, Rose-John S . Structural and functional studies on the human hepatic interleukin-6 receptor. Molecular cloning and overexpression in HepG2 cells . Biochem. J. . 277 (Pt 3) . Pt 3 . 659–64 . 1991 . 10.1042/bj2770659 . 1872801 . 1151293 .
• Szpirer J, Szpirer C, Rivière M, Houart C, Baumann M, Fey GH, Poli V, Cortese R, Islam MQ, Levan G . The Interleukin-6-dependent DNA-binding protein gene (transcription factor 5: TCF5) maps to human chromosome 20 and rat chromosome 3, the IL6 receptor locus (IL6R) to human chromosome 1 and rat chromosome 2, and the rat IL6 gene to rat chromosome 4 . Genomics . 10 . 3 . 539–46 . 1991 . 1889804 . 10.1016/0888-7543(91)90433-F .
• Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T, Kishimoto T . Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis . J. Exp. Med. . 171 . 6 . 2001–9 . 1990 . 2112585 . 2187962 . 10.1084/jem.171.6.2001 .
• Snyers L, De Wit L, Content J . Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells . Proc. Natl. Acad. Sci. U.S.A. . 87 . 7 . 2838–42 . 1990 . 2157217 . 53786 . 10.1073/pnas.87.7.2838 . 1990PNAS...87.2838S . free .
• Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T . Molecular cloning and expression of an IL-6 signal transducer, gp130 . Cell . 63 . 6 . 1149–57 . 1990 . 2261637 . 10.1016/0092-8674(90)90411-7 . 30852638 .
• Novick D, Engelmann H, Wallach D, Rubinstein M . Soluble cytokine receptors are present in normal human urine . J. Exp. Med. . 170 . 4 . 1409–14 . 1989 . 2529343 . 2189483 . 10.1084/jem.170.4.1409 .
• Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T . Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 . Cell . 58 . 3 . 573–81 . 1989 . 2788034 . 10.1016/0092-8674(89)90438-8 . 41245022 .
• Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T . Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor . Science . 241 . 4867 . 825–8 . 1988 . 3136546 . 10.1126/science.3136546 . 1988Sci...241..825Y .
• Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M, Matsumoto A, Yamamoto M, Yamamoto N . Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism . Eur. J. Immunol. . 24 . 8 . 1945–8 . 1994 . 8056053 . 10.1002/eji.1830240837 . 33258406 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Tamura T, Udagawa N, Takahashi N, Miyaura C, Tanaka S, Yamada Y, Koishihara Y, Ohsugi Y, Kumaki K, Taga T . Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6 . Proc. Natl. Acad. Sci. U.S.A. . 90 . 24 . 11924–8 . 1993 . 8265649 . 48097 . 10.1073/pnas.90.24.11924 . 1993PNAS...9011924T . free .
• Kluck PM, Wiegant J, Jansen RP, Bolk MW, Raap AK, Willemze R, Landegent JE . The human interleukin-6 receptor alpha chain gene is localized on chromosome 1 band q21 . Hum. Genet. . 90 . 5 . 542–4 . 1993 . 8428753 . 10.1007/BF00217455 . 33111417 .
• Chirmule N, Kalyanaraman VS, Lederman S, Oyaizu N, Yagura H, Yellin MJ, Chess L, Pahwa S . HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6 . J. Immunol. . 150 . 6 . 2478–86 . 1993 . 10.4049/jimmunol.150.6.2478 . 8450224 . 25128583 .
• Yawata H, Yasukawa K, Natsuka S, Murakami M, Yamasaki K, Hibi M, Taga T, Kishimoto T . Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130 . EMBO J. . 12 . 4 . 1705–12 . 1993 . 10.1002/j.1460-2075.1993.tb05815.x . 8467812 . 413384 .
• Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM . Identification of novel human WW domain-containing proteins by cloning of ligand targets . J. Biol. Chem. . 272 . 23 . 14611–6 . 1997 . 9169421 . 10.1074/jbc.272.23.14611 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, Nishinakamura R, Toyama Y, Yabe Y, Hori M, Takahashi N, Suda T . Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene . Endocrinology . 140 . 2 . 925–32 . 1999 . 9927325 . 10.1210/endo.140.2.6573 . free .

Notes and References

1. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell Melanoma Res . 21 . 6 . 665–76 . 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . free .
2. Web site: Entrez Gene: IL6R interleukin 6 receptor.
3. Schwantner A, Dingley AJ, Ozbek S, Rose-John S, Grötzinger J . Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy . J. Biol. Chem. . 279 . 1 . 571–6 . Jan 2004 . 14557255 . 10.1074/jbc.M311019200 . free .
4. Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, Rose-John S, Kallen KJ . Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF . J. Biol. Chem. . 278 . 11 . 9528–35 . Mar 2003 . 12643274 . 10.1074/jbc.M210044200 . free .
5. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T . Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 . Cell . 58 . 3 . 573–81 . Aug 1989 . 2788034 . 10.1016/0092-8674(89)90438-8 . 41245022 .
6. Schooltink H, Stoyan T, Roeb E, Heinrich PC, Rose-John S . Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes . FEBS Lett. . 314 . 3 . 280–4 . Dec 1992 . 1281789 . 10.1016/0014-5793(92)81489-9 . 39538295 . free .