Interleukin 5 receptor alpha subunit explained

Interleukin 5 receptor, alpha (IL5RA) also known as CD125 (Cluster of Differentiation 125) is a subunit of the Interleukin-5 receptor. IL5RA also denotes its human gene.^[1]

Function

The protein encoded by this gene is an interleukin 5 specific subunit of a heterodimeric cytokine receptor. The receptor is composed of a ligand specific alpha subunit and a signal transducing beta subunit shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2/GM-CSF), and interleukin 5 (IL5). The binding of this protein to IL5 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL5. This protein has been found to interact with syndecan binding protein (syntenin), which is required for IL5 mediated activation of the transcription factor SOX4. Six alternatively spliced transcript variants encoding three distinct isoforms have been reported.^[1]

Interactions

Interleukin 5 receptor alpha subunit has been shown to interact with:

• Interleukin 5,^{[2] [3] [4]}
• Janus kinase 2,^[5]
• Protein unc-119 homolog,^[6] and
• SDCBP^[7]

See also

• Cluster of differentiation
• Benralizumab
• Mepolizumab
• Reslizumab

Further reading

• Isobe M, Kumura Y, Murata Y, Takaki S, Tominaga A, Takatsu K, Ogita Z . Localization of the gene encoding the alpha subunit of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26. . Genomics . 14 . 3 . 755–8 . 1992 . 1427903 . 10.1016/S0888-7543(05)80180-6 .
• Tuypens T, Plaetinck G, Baker E, Sutherland G, Brusselle G, Fiers W, Devos R, Tavernier J . Organization and chromosomal localization of the human interleukin 5 receptor alpha-chain gene. . Eur. Cytokine Netw. . 3 . 5 . 451–9 . 1993 . 1477296 .
• Tavernier J, Tuypens T, Plaetinck G, Verhee A, Fiers W, Devos R . Molecular basis of the membrane-anchored and two soluble isoforms of the human interleukin 5 receptor alpha subunit. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 15 . 7041–5 . 1992 . 1495999 . 49641 . 10.1073/pnas.89.15.7041 . 1992PNAS...89.7041T . free .
• Scott HS, Guo XH, Hopwood JJ, Morris CP . Structure and sequence of the human alpha-L-iduronidase gene. . Genomics . 13 . 4 . 1311–3 . 1992 . 1505961 . 10.1016/0888-7543(92)90053-U .
• 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 . 2119102 . 10.1084/jem.175.2.341 .
• 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 . 1991 . 1833065 . 10.1016/0092-8674(91)90040-6 . 54277241 .
• Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R . Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. . J. Biol. Chem. . 270 . 16 . 9459–71 . 1995 . 7721873 . 10.1074/jbc.270.16.9459 . free .
• Sun Z, Yergeau DA, Tuypens T, Tavernier J, Paul CC, Baumann MA, Tenen DG, Ackerman SJ . Identification and characterization of a functional promoter region in the human eosinophil IL-5 receptor alpha subunit gene. . J. Biol. Chem. . 270 . 3 . 1462–71 . 1995 . 7836416 . 10.1074/jbc.270.3.1462 . free .
• Hori K, Hirashima M, Ueno M, Matsuda M, Waga S, Tsurufuji S, Yodoi J . Regulation of eosinophil migration by adult T cell leukemia-derived factor. . J. Immunol. . 151 . 10 . 5624–30 . 1993 . 10.4049/jimmunol.151.10.5624 . 8228251 . free .
• Huston MM, Moore JP, Mettes HJ, Tavana G, Huston DP . Human B cells express IL-5 receptor messenger ribonucleic acid and respond to IL-5 with enhanced IgM production after mitogenic stimulation with Moraxella catarrhalis. . J. Immunol. . 156 . 4 . 1392–401 . 1996 . 10.4049/jimmunol.156.4.1392 . 8568239 . free .
• Monahan J, Siegel N, Keith R, Caparon M, Christine L, Compton R, Cusik S, Hirsch J, Huynh M, Devine C, Polazzi J, Rangwala S, Tsai B, Portanova J . Attenuation of IL-5-mediated signal transduction, eosinophil survival, and inflammatory mediator release by a soluble human IL-5 receptor. . J. Immunol. . 159 . 8 . 4024–34 . 1997 . 10.4049/jimmunol.159.8.4024 . 9378992 . 22709807 .
• 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 . 1998 . 9516124 . 10.1182/blood.V91.7.2264. free .
• Tavernier J, Van der Heyden J, Verhee A, Brusselle G, Van Ostade X, Vandekerckhove J, North J, Rankin SM, Kay AB, Robinson DS . Interleukin 5 regulates the isoform expression of its own receptor alpha-subunit. . Blood . 95 . 5 . 1600–7 . 2000 . 10688814 . 10.1182/blood.V95.5.1600.005k22_1600_1607.
• Czabotar PE, Holland J, Sanderson CJ . Identification of regions within the third FnIII-like domain of the IL-5Ralpha involved in IL-5 interaction. . Cytokine . 12 . 7 . 867–73 . 2000 . 10880230 . 10.1006/cyto.1999.0663 .
• Plugariu CG, Wu SJ, Zhang W, Chaiken I . Multisite mutagenesis of interleukin 5 differentiates sites for receptor recognition and receptor activation. . Biochemistry . 39 . 48 . 14939–49 . 2001 . 11101310 . 10.1021/bi001467p .
• Geijsen N, Uings IJ, Pals C, Armstrong J, McKinnon M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ . Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein. . Science . 293 . 5532 . 1136–8 . 2001 . 11498591 . 10.1126/science.1059157 . 28003281 .
• Upham JW, Sehmi R, Hayes LM, Howie K, Lundahl J, Denburg JA . Retinoic acid modulates IL-5 receptor expression and selectively inhibits eosinophil-basophil differentiation of hemopoietic progenitor cells. . J. Allergy Clin. Immunol. . 109 . 2 . 307–13 . 2002 . 11842302 . 10.1067/mai.2002.121527 . free .
• Rizzo CA, Yang R, Greenfeder S, Egan RW, Pauwels RA, Hey JA . The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness. . J. Allergy Clin. Immunol. . 109 . 3 . 404–9 . 2002 . 11897983 . 10.1067/mai.2002.122459 .
• Scibek JJ, Evergren E, Zahn S, Canziani GA, Van Ryk D, Chaiken IM . Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c) interaction with IL5:IL5R(alpha) complexes. . Anal. Biochem. . 307 . 2 . 258–65 . 2003 . 12202242 . 10.1016/S0003-2697(02)00043-X .
• Liu LY, Sedgwick JB, Bates ME, Vrtis RF, Gern JE, Kita H, Jarjour NN, Busse WW, Kelly EA . Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increased soluble IL-5 receptor alpha in the airway after allergen challenge. . J. Immunol. . 169 . 11 . 6452–8 . 2002 . 12444154 . 10.4049/jimmunol.169.11.6452 . free .

Notes and References

1. Web site: Entrez Gene: IL5RA interleukin 5 receptor, alpha.
2. Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF . Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF . EMBO J. . 13 . 21 . 5176–85 . Nov 1994 . 7957082 . 395466 . 10.1002/j.1460-2075.1994.tb06848.x.
3. Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R . Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins . J. Biol. Chem. . 270 . 16 . 9459–71 . Apr 1995 . 7721873 . 10.1074/jbc.270.16.9459. free .
4. 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 . Feb 1992 . 1732409 . 2119102 . 10.1084/jem.175.2.341.
5. 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 . Apr 1998 . 9516124 . 10.1182/blood.V91.7.2264. free .
6. Cen O, Gorska MM, Stafford SJ, Sur S, Alam R . Identification of UNC119 as a novel activator of SRC-type tyrosine kinases . J. Biol. Chem. . 278 . 10 . 8837–45 . Mar 2003 . 12496276 . 10.1074/jbc.M208261200 . free .
7. Geijsen N, Uings IJ, Pals C, Armstrong J, McKinnon M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ . Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein . Science . 293 . 5532 . 1136–8 . Aug 2001 . 11498591 . 10.1126/science.1059157 . 28003281 .