Interleukin 20 receptor, alpha subunit explained

Interleukin 20 receptor, alpha subunit, is a subunit of the interleukin-20 receptor, the interleukin-26 receptor, and the interleukin-24 receptor.^[1] The interleukin 20 receptor, alpha subunit is also referred to as IL20R1^[2] or IL20RA.^[3] The IL20RA receptor is involved in both pro-inflammatory and anti-inflammatory responses, signaling through the JAK-STAT pathway.^[1]

IL20RA is found in the skin, lungs, ovaries, testes and placenta, with low gene expression in the intestine and liver. IL20RB is found in many organ resident effector cells such as keratinocytes at the skin epidermis, osteoclasts, found in bones, and epithelial cells of the intestine and trachea. IL20RA is also found in some immune cells.^[4]

Structure and function

IL20RA is an alpha-chain with a long intracellular domain. IL20RA, along with the IL-20 receptor, beta subunit, form the heterodimeric interleukin-20 receptor, which binds the cytokines IL-19, IL-20 and IL-24. IL20RA also forms a complex with the IL-10 receptor, beta subunit, which binds the cytokine IL-26.^[1]

Signaling

Receptors made up of IL20RA signal through a JAK-STAT signaling pathway.^[1] In this pathway, after a cytokine binds IL20RA and the beta subunit, JAKs linked to intracellular domains of IL20R activate and phosphorylate tyrosine residues found in the longer alpha chains of IL20RA. STAT then binds to docking sites created by JAK phosphorylation and becomes phosphorylated by JAK. STATs then dimerize and move to the nucleus to act as transcription factors. The specific genes expressed are dependent on the specific JAK, STAT, as well as by SOCS proteins, which can inhibit the JAK-STAT signal, regulating it.where the transcription factor STAT3 binds to IL20RA and STAT3 becomes activated.^[1] IL20RA has multiple docking sites for STAT3.^[5]

Link to Immune System and Disease

Research indicates that IL20RA is found in some immune cells. For example, IL20RA is sometimes found in lung macrophages. Research indicates that IL20RA presence may be related to disease. In people with rheumatoid arthiritis, IL20RA is present in blood monocytes.^[4]

IL20RA has also been linked with psoriasis, and atherosclerosis, all diseases associated with inflammation. The specific role of IL20RA in these diseases is unknown.^[3]

Further reading

• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Xie MH . Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R . J. Biol. Chem. . 275 . 40 . 31335–31339 . 2000 . 10875937 . 10.1074/jbc.M005304200 . vanc. Aggarwal S . Ho WH . 3 . Foster . J . Zhang . Z . Stinson . J . Wood . WI . Goddard . AD . Gurney . AL . free .
• Blumberg H . Interleukin 20: discovery, receptor identification, and role in epidermal function . Cell . 104 . 1 . 9–19 . 2001 . 11163236 . 10.1016/S0092-8674(01)00187-8 . vanc. Conklin D . Xu WF . 3 . Grossmann . Angelika . Brender . Ty . Carollo . Susan . Eagan . Maribeth . Foster . Don . Haldeman . Betty A . 7460710 . free .
• Dumoutier L . Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types . J. Immunol. . 167 . 7 . 3545–9 . 2001 . 11564763 . 10.4049/jimmunol.167.7.3545. vanc. Leemans C . Lejeune D . 3 . Kotenko . SV . Renauld . JC . free.
• Wang M . Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2 . J. Biol. Chem. . 277 . 9 . 7341–7347 . 2002 . 11706020 . 10.1074/jbc.M106043200 . vanc. Tan Z . Zhang R . 3 . Kotenko . SV . Liang . P . free .
• Parrish-Novak J . Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions . J. Biol. Chem. . 277 . 49 . 47517–47523 . 2003 . 12351624 . 10.1074/jbc.M205114200 . vanc. Xu W . Brender T . 3 . Yao . L . Jones . C . West . J . Brandt . C . Jelinek . L . Madden . K . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Clark HF . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Res. . 13 . 10 . 2265–2270 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 . vanc. Gurney AL . Abaya E . 3 . Baker . K . Baldwin . D . Brush . J . Chen . J . Chow . B . Chui . C .
• Mungall AJ . The DNA sequence and analysis of human chromosome 6 . Nature . 425 . 6960 . 805–811 . 2003 . 14574404 . 10.1038/nature02055 . vanc. Palmer SA . Sims SK . 3 . Edwards . C. A. . Ashurst . J. L. . Wilming . L. . Jones . M. C. . Horton . R. . Hunt . S. E. . free .
• Pletnev S . Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20 . Biochemistry . 42 . 43 . 12617–12624 . 2003 . 14580208 . 10.1021/bi0354583 . vanc. Magracheva E . Kozlov S . 3 . Tobin . Gregory . Kotenko . Sergei V. . Wlodawer . Alexander . Zdanov . Alexander .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–45 . 2004 . 14702039 . 10.1038/ng1285 . vanc. Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Sheikh F . Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2 . J. Immunol. . 172 . 4 . 2006–10 . 2004 . 14764663 . 10.4049/jimmunol.172.4.2006. vanc. Baurin VV . Lewis-Antes A . 3 . Shah . NK . Smirnov . SV . Anantha . S . Dickensheets . H . Dumoutier . L . Renauld . JC . free .
• Hör S . The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains . J. Biol. Chem. . 279 . 32 . 33343–33351 . 2004 . 15178681 . 10.1074/jbc.M405000200 . vanc. Pirzer H . Dumoutier L . 3 . Bauer . F . Wittmann . S . Sticht . H . Renauld . JC . De Waal Malefyt . R . Fickenscher . H . free .
• Zhang Z, Henzel WJ . Signal peptide prediction based on analysis of experimentally verified cleavage sites . Protein Sci. . 13 . 10 . 2819–2824 . 2005 . 15340161 . 10.1110/ps.04682504 . 2286551 .

Notes and References

1. Wegenka . Ursula Maria . 2010-10-01 . IL-20: Biological functions mediated through two types of receptor complexes . Cytokine & Growth Factor Reviews . IL-10 Family of Cytokines . en . 21 . 5 . 353–363 . 10.1016/j.cytogfr.2010.08.001 . 20864382 . 1359-6101.
2. Wirtz . Mary K. . Keller . Kate E. . 2016 . The Role of the IL-20 Subfamily in Glaucoma . Mediators of Inflammation . 2016 . 1–8 . 10.1155/2016/4083735 . 26903709 . 0962-9351. 4745377 . free .
3. Rutz . Sascha . Wang . Xiaoting . Ouyang . Wenjun . December 2014 . The IL-20 subfamily of cytokines — from host defence to tissue homeostasis . Nature Reviews Immunology . en . 14 . 12 . 783–795 . 10.1038/nri3766 . 25421700 . 29114703 . 1474-1741.
4. Kragstrup . Tue W. . Andersen . Thomas . Heftdal . Line D. . Hvid . Malene . Gerwien . Jens . Sivakumar . Pallavur . Taylor . Peter C. . Senolt . Ladislav . Deleuran . Bent . 2018-09-25 . The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis . Frontiers in Immunology . 9 . 2226 . 10.3389/fimmu.2018.02226 . 30319661 . 1664-3224. 6167463 . free .
5. Blumberg . Hal . Conklin . Darrell . Xu . WenFeng . Grossmann . Angelika . Brender . Ty . Carollo . Susan . Eagan . Maribeth . Foster . Don . Haldeman . Betty A . Hammond . Angie . Haugen . Harald . Jelinek . Laura . Kelly . James D . Madden . Karen . Maurer . Mark F . 2001-01-12 . Interleukin 20: Discovery, Receptor Identification, and Role in Epidermal Function . Cell . en . 104 . 1 . 9–19 . 10.1016/S0092-8674(01)00187-8 . 11163236 . 0092-8674. free .