Interleukin-5 receptor
| interleukin 5 receptor, alpha | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | IL5RA | ||||||
| Alt. symbols | IL5R | ||||||
| NCBI gene | 3568 | ||||||
| HGNC | 6017 | ||||||
| OMIM | 147851 | ||||||
| RefSeq | NM_175725 | ||||||
| UniProt | Q01344 | ||||||
| Other data | |||||||
| Locus | Chr. 3p26-p24 | ||||||
| |||||||
| colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | CSF2RB | ||||||
| Alt. symbols | IL3RB | ||||||
| NCBI gene | 1439 | ||||||
| HGNC | 2436 | ||||||
| OMIM | 138981 | ||||||
| RefSeq | NM_000395 | ||||||
| UniProt | P32927 | ||||||
| Other data | |||||||
| Locus | Chr. 22q12.2-13.1 | ||||||
| |||||||
Theinterleukin-5 receptoris atype I cytokine receptor.It is a heterodimer of theinterleukin 5 receptor alpha subunitandCSF2RB.[1][2]
The IL-5 receptor (IL-5R) belongs to thetype I cytokine receptorfamily and is a heterodimer composed of twopolypeptidechains, one α subunit, which binds IL-5 and confers upon the receptor cytokine specificity, and one β subunit, which contains thesignal transductiondomains.
α-subunit
[edit]The IL-5Rα chain is exclusively expressed by eosinophils, somebasophilsand murine B1 cells or B cell precursors.[3]Like many other cytokine receptors,alternative splicingof the α-chain gene results in expression of either a membrane bound or soluble form of the bα-chain. The soluble form does not lead to signal transduction and therefore has an antagonistic effect on IL-5 signaling. Both monomeric forms of IL-5Rα are low affinity receptors, while dimerization with the β-chain produces a high affinity receptor.[4]In either case, the α-chain exclusively binds IL-5 and the intra-cellular portion of IL-5Rα is associated withJanus kinase(JAK) 2, aprotein tyrosine-kinaseessential in IL-5 signal transduction.[5][6]
β-subunit
[edit]The β-subunit of the IL-5 receptor is responsible for signal transduction and contains several intracellular signaling domains. Unlike the α-chain, the β-chain does not bind IL-5, is not specific to this cytokine, and is expressed on practically allleukocytes.In fact, the β-subunit of the IL-5 receptor is also found inIL-3andGM-CSFreceptors where it is associated withIL-3RαandGM-CSFRαsubunits respectively.[7]Therefore, it is known as the common β receptor or βc. As with the IL-5Rα subunit, the β subunit’scytoplasmicdomain is constitutively associated withJAK2,[8]as well asLYN,[9]another tyrosine kinase, which are both essential for IL-5 signal transduction.[10]
Drug target
[edit]Three monoclonal antibodies are available to target IL-5R.Benralizumabbinds to IL-5Ra, whilemepolizumabandreslizumabbind to IL-5, preventing it from binding to IL-5Ra.
References
[edit]- ^Takatsu K, Tominaga A (1991). "Interleukin 5 and its receptor".Prog. Growth Factor Res.3(2): 87–102.doi:10.1016/S0955-2235(05)80001-8.PMID1773042.
- ^Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K (1992)."Molecular cloning and expression of the human interleukin 5 receptor".J. Exp. Med.175(2): 341–51.doi:10.1084/jem.175.2.341.PMC2119102.PMID1732409.
- ^Geijsen N, Koenderman L, Coffer PJ (March 2001). "Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family".Cytokine Growth Factor Rev.12(1): 19–25.doi:10.1016/S1359-6101(00)00019-8.PMID11312115.
- ^Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G (September 1991). "A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF".Cell.66(6): 1175–84.doi:10.1016/0092-8674(91)90040-6.PMID1833065.S2CID54277241.
- ^Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K (April 1998)."JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation".Blood.91(7): 2264–71.doi:10.1182/blood.V91.7.2264.PMID9516124.
- ^Takaki S, Kanazawa H, Shiiba M, Takatsu K (November 1994)."A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction".Mol. Cell. Biol.14(11): 7404–13.doi:10.1128/mcb.14.11.7404.PMC359275.PMID7935454.
- ^Martinez-Moczygemba M, Huston DP (October 2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF".J. Allergy Clin. Immunol.112(4): 653–65, quiz 666.doi:10.1016/j.jaci.2003.08.015.PMID14564341.
- ^Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A, Griffin JD, Ihle JN (July 1994)."JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region".Mol. Cell. Biol.14(7): 4335–41.doi:10.1128/mcb.14.7.4335.PMC358804.PMID8007942.
- ^Li Y, Shen BF, Karanes C, Sensenbrenner L, Chen B (August 1995). "Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e)".J. Immunol.155(4): 2165–74.doi:10.4049/jimmunol.155.4.2165.PMID7636265.
- ^Sato N, Sakamaki K, Terada N, Arai K, Miyajima A (November 1993)."Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling".EMBO J.12(11): 4181–9.doi:10.1002/j.1460-2075.1993.tb06102.x.PMC413712.PMID8223433.
External links
[edit]- Receptors,+Interleukin-5at the U.S. National Library of MedicineMedical Subject Headings(MeSH)