Interleukin-5 receptor

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]

interleukin 5 receptor, alpha
Identifiers
SymbolIL5RA
Alt. symbolsIL5R
NCBI gene3568
HGNC6017
OMIM147851
RefSeqNM_175725
UniProtQ01344
Other data
LocusChr. 3 p26-p24
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StructuresSwiss-model
DomainsInterPro
colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage)
Identifiers
SymbolCSF2RB
Alt. symbolsIL3RB
NCBI gene1439
HGNC2436
OMIM138981
RefSeqNM_000395
UniProtP32927
Other data
LocusChr. 22 q12.2-13.1
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StructuresSwiss-model
DomainsInterPro

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.

References
  1. 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. PMID 1773042.
  2. 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. PMC 2119102. PMID 1732409.
  3. 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. PMID 11312115.
  4. 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. PMID 1833065. S2CID 54277241.
  5. 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. PMID 9516124.
  6. 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. PMC 359275. PMID 7935454.
  7. 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. PMID 14564341.
  8. 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. PMC 358804. PMID 8007942.
  9. 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. PMID 7636265.
  10. 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. PMC 413712. PMID 8223433.
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