Interleukin 20 receptor, alpha subunit
Interleukin 20 receptor, alpha subunit, is a subunit of the interleukin-20 receptor, the interleukin-26 receptor, and the interleukin-24 receptor.[5] The interleukin 20 receptor, alpha subunit is also referred to as IL20R1[6] or IL20RA.[7] The IL20RA receptor is involved in both pro-inflammatory and anti-inflammatory responses, signaling through the JAK-STAT pathway.[5]
| IL20RA | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | IL20RA, CRF2-8, IL-20R-alpha, IL-20R1, IL-20RA, Interleukin 20 receptor, alpha subunit, interleukin 20 receptor subunit alpha | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 605620 MGI: 3605069 HomoloGene: 8685 GeneCards: IL20RA | ||||||||||||||||||||||||||||||||||||||||||||||||||
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IL20RA is found in the skin, lungs, ovaries, testes and placenta, with low gene expression in the intestine and liver.[7] 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.[8]
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.[5]
Signaling
Receptors made up of IL20RA signal through a JAK-STAT signaling pathway.[5] 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][9]
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.[8]
IL20RA has also been linked with psoriasis, and atherosclerosis, all diseases associated with inflammation. The specific role of IL20RA in these diseases is unknown.[7]
References
- GRCh38: Ensembl release 89: ENSG00000016402 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000020007 - 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.
- 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. 21 (5): 353–363. doi:10.1016/j.cytogfr.2010.08.001. ISSN 1359-6101. PMID 20864382.
- Wirtz, Mary K.; Keller, Kate E. (2016). "The Role of the IL-20 Subfamily in Glaucoma". Mediators of Inflammation. 2016: 1–8. doi:10.1155/2016/4083735. ISSN 0962-9351. PMC 4745377. PMID 26903709.
- Rutz, Sascha; Wang, Xiaoting; Ouyang, Wenjun (December 2014). "The IL-20 subfamily of cytokines — from host defence to tissue homeostasis". Nature Reviews Immunology. 14 (12): 783–795. doi:10.1038/nri3766. ISSN 1474-1741. PMID 25421700. S2CID 29114703.
- 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. doi:10.3389/fimmu.2018.02226. ISSN 1664-3224. PMC 6167463. PMID 30319661.
- 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. 104 (1): 9–19. doi:10.1016/S0092-8674(01)00187-8. ISSN 0092-8674. PMID 11163236.
Further reading
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Xie MH, Aggarwal S, Ho WH, et al. (2000). "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. doi:10.1074/jbc.M005304200. PMID 10875937.
- Blumberg H, Conklin D, Xu WF, et al. (2001). "Interleukin 20: discovery, receptor identification, and role in epidermal function". Cell. 104 (1): 9–19. doi:10.1016/S0092-8674(01)00187-8. PMID 11163236. S2CID 7460710.
- Dumoutier L, Leemans C, Lejeune D, et al. (2001). "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. doi:10.4049/jimmunol.167.7.3545. PMID 11564763.
- Wang M, Tan Z, Zhang R, et al. (2002). "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. doi:10.1074/jbc.M106043200. PMID 11706020.
- Parrish-Novak J, Xu W, Brender T, et al. (2003). "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. doi:10.1074/jbc.M205114200. PMID 12351624.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Clark HF, Gurney AL, Abaya E, et al. (2003). "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. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
- Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–811. doi:10.1038/nature02055. PMID 14574404.
- Pletnev S, Magracheva E, Kozlov S, et al. (2003). "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. doi:10.1021/bi0354583. PMID 14580208.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
- Sheikh F, Baurin VV, Lewis-Antes A, et al. (2004). "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. doi:10.4049/jimmunol.172.4.2006. PMID 14764663.
- Hör S, Pirzer H, Dumoutier L, et al. (2004). "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. doi:10.1074/jbc.M405000200. PMID 15178681.
- Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–2824. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.