Interleukin-5 receptor

α-subunit

The IL-5Rα chain is exclusively expressed by eosinophils, some basophils and murine B1 cells or B cell precursors. 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. 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.

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. 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, as well as LYN, another tyrosine kinase, which are both essential for IL-5 signal transduction.

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

References

1. (1991). "Interleukin 5 and its receptor". Prog. Growth Factor Res..
2. (1992). "Molecular cloning and expression of the human interleukin 5 receptor". J. Exp. Med..
3. (March 2001). "Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family". Cytokine Growth Factor Rev..
4. (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.
5. (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.
6. (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..
7. (October 2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF". J. Allergy Clin. Immunol..
8. (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..
9. (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..
10. (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..