The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4R
Interleukin-4 receptor alpha chain, N-terminal | |||||||||
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Identifiers | |||||||||
Symbol | IL4Ra_N | ||||||||
Pfam | PF09238 | ||||||||
InterPro | IPR015319 | ||||||||
SCOP2 | 1iar / SCOPe / SUPFAM | ||||||||
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Function
editThis gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE antibody production in B cells. Among T cells, the encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. Two transcript variants encoding different isoforms, a membrane-bound and a soluble form, have been found for this gene.[6] Interactions of IL-4 with TNF
The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of macrophages results in the alternative activation of those macrophages. Alternatively activated macrophages (AAM
Interactions
editInterleukin-4 receptor has been shown to interact with SHC1.[9][10]
Structure
editThe N-terminal (extracellular) portion of interleukin-4 receptor is related in overall topology to fibronectin type III modules and folds into a sandwich comprising seven antiparallel beta sheets arranged in a three-strand and a four-strand beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response.[11]
See also
editReferences
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000077238 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030748 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ McCormick SM (14 July 2015). "Commentary: IL-4 and IL-13 receptors and signaling". Cytokine. 75 (1): 38–50. doi:10.1016/j.cyto.2015.05.023. PMC 4546937. PMID 26187331 – via Elsevier ScienceDirect.
- ^ "Entrez Gene: IL4R interleukin 4 receptor".
- ^ Thornhill MH, Wellicome SM, Mahiouz DL, Lanchbury J, Kyanaung U, Haskard DO (Jan 1991). "Tumor-necrosis-factor combines with IL-4 or IFN-gamma to selectively enhance endothelial-cell adhesiveness for T-cells-the contribution of vascular cell-adhesion molecule-1-dependent and molecule-1-independent binding mechanisms". Journal of Immunology. 146 (2): 592–598. doi:10.4049/jimmunol.146.2.592. PMID 1702807.
- ^ Tundup S, Srivastava L, Harn DA (April 2012). "Polarization of host immune responses by helminth-expressed glycans". Ann. N. Y. Acad. Sci. 1253 (1): E1–E13. Bibcode:2012NYASA1253E...1T. doi:10.1111/j.1749-6632.2012.06618.x. PMID 22974465. S2CID 43256244.
- ^ Ikizawa K, Yanagihara Y (February 2000). "Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line". Biochem. Biophys. Res. Commun. 268 (1): 54–9. doi:10.1006/bbrc.2000.2080. PMID 10652211.
- ^ Kashiwada M, Giallourakis CC, Pan PY, Rothman PB (December 2001). "Immunoreceptor tyrosine-based inhibitory motif of the IL-4 receptor associates with SH2-containing phosphatases and regulates IL-4-induced proliferation". J. Immunol. 167 (11): 6382–7. doi:10.4049/jimmunol.167.11.6382. PMID 11714803.
- ^ Hage T, Sebald W, Reinemer P (April 1999). "Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface". Cell. 97 (2): 271–81. doi:10.1016/S0092-8674(00)80736-9. PMID 10219247. S2CID 18795930.
Further reading
edit- Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999). "The IL-4 receptor: signaling mechanisms and biologic functions". Annu. Rev. Immunol. 17 (1): 701–38. doi:10.1146/annurev.immunol.17.1.701. PMID 10358772.
- Jiang H, Harris MB, Rothman P (2000). "IL-4/IL-13 signaling beyond JAK/STAT". J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. doi:10.1067/mai.2000.107604. PMID 10856136.
External links
edit- CD124+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha