Interleukin-5 receptor explained
| interleukin 5 receptor, alpha |
| Hgncid: | 6017 |
| Symbol: | IL5RA |
| Altsymbols: | IL5R |
| Entrezgene: | 3568 |
| Omim: | 147851 |
| Refseq: | NM_175725 |
| Uniprot: | Q01344 |
| Chromosome: | 3 |
| Arm: | p |
| Band: | 26 |
| Locussupplementarydata: | -p24 |
The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB.[1] [2]
The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor family and is a heterodimer composed of two polypeptide chains, one α subunit, which binds IL-5 and confers upon the receptor cytokine specificity, and one β subunit, which contains the signal transduction domains.
α-subunit
The IL-5Rα chain is exclusively expressed by eosinophils, some basophils and murine B1 cells or B cell precursors.[3] Like many other cytokine receptors, alternative splicing of 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 with Janus kinase (JAK) 2, a protein tyrosine-kinase essential in IL-5 signal transduction.[5] [6]
β-subunit
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 all leukocytes. In fact, the β-subunit of the IL-5 receptor is also found in IL-3 and GM-CSF receptors where it is associated with IL-3Rα and GM-CSFRα subunits respectively.[7] Therefore, it is known as the common β receptor or βc. As with the IL-5Rα subunit, the β subunit’s cytoplasmic domain is constitutively associated with JAK2,[8] as well as LYN,[9] another tyrosine kinase, which are both essential for IL-5 signal transduction.[10]
Drug target
Three monoclonal antibodies are available to target IL-5R. Benralizumab binds to IL-5Ra, while mepolizumab and reslizumab bind to IL-5, preventing it from binding to IL-5Ra.
Notes and References
- Takatsu K, Tominaga A . Interleukin 5 and its receptor . Prog. Growth Factor Res. . 3 . 2 . 87–102 . 1991 . 1773042 . 10.1016/S0955-2235(05)80001-8 .
- Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K . Molecular cloning and expression of the human interleukin 5 receptor . J. Exp. Med. . 175 . 2 . 341–51 . 1992 . 1732409 . 10.1084/jem.175.2.341 . 2119102 .
- Geijsen N, Koenderman L, Coffer PJ . 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 . March 2001 . 11312115 . 10.1016/S1359-6101(00)00019-8 .
- Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G . 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 . September 1991 . 1833065 . 10.1016/0092-8674(91)90040-6 . 54277241 .
- Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K . 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 . April 1998 . 9516124 . 10.1182/blood.V91.7.2264. free .
- Takaki S, Kanazawa H, Shiiba M, Takatsu K . 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 . November 1994 . 7935454 . 359275 . 10.1128/mcb.14.11.7404.
- Martinez-Moczygemba M, Huston DP . Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF . J. Allergy Clin. Immunol. . 112 . 4 . 653–65; quiz 666 . October 2003 . 14564341 . 10.1016/j.jaci.2003.08.015 .
- Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A, Griffin JD, Ihle JN . 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 . July 1994 . 8007942 . 358804 . 10.1128/mcb.14.7.4335.
- Li Y, Shen BF, Karanes C, Sensenbrenner L, Chen B . 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 . August 1995 . 10.4049/jimmunol.155.4.2165 . 7636265 .
- Sato N, Sakamaki K, Terada N, Arai K, Miyajima A . 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 . November 1993 . 8223433 . 413712 . 10.1002/j.1460-2075.1993.tb06102.x.
