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.
^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.
^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.
