CD124; interleukin-4 receptor alpha chain; IL-4R-alpha; sIL4Ralpha/prot; IL-4-binding protein; IL4-BP (IL4R, 582J21, IL4RA)
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Function
- subunit for both IL-4 receptor & IL-13 receptor
- couples to the JAK1/2/3-STAT6 pathway
- soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation & IL5 up-regulation by T-cells
- interacts with the IL13/IL13RA1 complex to form a type 2 receptor
- interacts with PIK3C3 (putative)
- interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 & INPP5D/SHIP (putative)
- interacts with JAK1 through a Box 1-containing region
- in Th1 cells, binds N-terminal 50 amino acids of SOCS5, which inhibits JAK1 interaction, STAT6 activation & Th2 cell differentiation
- SOCS5 interaction is independent of Tur phosphorylation (putative)
- on IL4 binding, phosphorylated on C-terminal Tyr.
- phosphorylation on any one of Tyr-575, Tyr-603 or Tyr-631, is required for STAT6-induced gene induction
- the soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase
Structure
- the extracellular domain represents the IL4 binding protein (IL4BP)
- the WSXWS motif appears to be necessary for proper protein folding, efficient intracellular transport & cell-surface receptor binding
- the box 1 motif is required for JAK interaction &/or activation
- contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM)
- phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
- belongs to the type I cytokine receptor family, type 4 subfamily
- contains 1 fibronectin F3 module
Compartment
Alternative splicing
named isoforms=2
Expression
Pathology
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P24394.html
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/il4r/
- ↑ SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=IL4R
- ↑ Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8048164
- ↑ Klaus GG, Harnett MM. Cross-talk between B cell surface immunoglobulin and interleukin 4 receptors: the role of protein kinase C and Ca2(+)-mediated signals. Eur J Immunol. 1990 Oct;20(10):2301-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2173663
- ↑ Taga T & Kishimoto T Cytokine receptors and signal transduction FASEB J 6:3387 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1334470
- ↑ Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8048164