“Interleukin-5 receptor”的意思、由来-开放百科全书

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.

References

1. ^{{cite journal |vauthors=Takatsu K, Tominaga A | title = Interleukin 5 and its receptor | journal = Prog. Growth Factor Res. | volume = 3 | issue = 2 | pages = 87–102 | year = 1991 | pmid = 1773042 | doi = 10.1016/S0955-2235(05)80001-8 }}
2. ^{{cite journal |vauthors=Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K | title = Molecular cloning and expression of the human interleukin 5 receptor | journal = J. Exp. Med. | volume = 175 | issue = 2 | pages = 341–51 | year = 1992 | pmid = 1732409 | doi = 10.1084/jem.175.2.341 | pmc = 2119102 }}
3. ^{{cite journal |vauthors=Geijsen N, Koenderman L, Coffer PJ | title = Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family | journal = Cytokine Growth Factor Rev. | volume = 12 | issue = 1 | pages = 19–25 |date=March 2001 | pmid = 11312115 | doi =10.1016/S1359-6101(00)00019-8 }}
4. ^{{cite journal |vauthors=Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G | title = 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 | journal = Cell | volume = 66 | issue = 6 | pages = 1175–84 |date=September 1991 | pmid = 1833065 | doi =10.1016/0092-8674(91)90040-6 }}
5. ^{{cite journal |vauthors=Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K | title = JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation | journal = Blood | volume = 91 | issue = 7 | pages = 2264–71 |date=April 1998 | pmid = 9516124 | doi = }}
6. ^{{cite journal |vauthors=Takaki S, Kanazawa H, Shiiba M, Takatsu K | title = A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction | journal = Mol. Cell. Biol. | volume = 14 | issue = 11 | pages = 7404–13 |date=November 1994 | pmid = 7935454 | pmc = 359275 | doi = }}
7. ^{{cite journal |vauthors=Martinez-Moczygemba M, Huston DP | title = Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF | journal = J. Allergy Clin. Immunol. | volume = 112 | issue = 4 | pages = 653–65; quiz 666 |date=October 2003 | pmid = 14564341 | doi = 10.1016/j.jaci.2003.08.015 }}
8. ^{{cite journal |vauthors=Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A, Griffin JD, Ihle JN | title = JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region | journal = Mol. Cell. Biol. | volume = 14 | issue = 7 | pages = 4335–41 |date=July 1994 | pmid = 8007942 | pmc = 358804 | doi = }}
9. ^{{cite journal |vauthors=Li Y, Shen BF, Karanes C, Sensenbrenner L, Chen B | title = 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) | journal = J. Immunol. | volume = 155 | issue = 4 | pages = 2165–74 |date=August 1995 | pmid = 7636265 | doi = }}
10. ^{{cite journal |vauthors=Sato N, Sakamaki K, Terada N, Arai K, Miyajima A | title = Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling | journal = EMBO J. | volume = 12 | issue = 11 | pages = 4181–9 |date=November 1993 | pmid = 8223433 | pmc = 413712 | doi = }}

α-subunit

β-subunit

Drug target

References

External links