Interleukin 8 receptor, alpha

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Chemokine (C-X-C motif) receptor 1

Rendering of 1ILP
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CXCR1 ; C-C; C-C-CKR-1; CD128; CD181; CDw128a; CKR-1; CMKAR1; IL8R1; IL8RA; IL8RBA
External IDs OMIM146929 MGI2448715 HomoloGene68074 IUPHAR: CXCR1 ChEMBL: 4029 GeneCards: CXCR1 Gene
RNA expression pattern
PBB GE IL8RA 207094 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3577 227288
Ensembl ENSG00000163464 ENSMUSG00000048480
UniProt P25024 Q810W6
RefSeq (mRNA) NM_000634 NM_178241
RefSeq (protein) NP_000625 NP_839972
Location (UCSC) Chr 2:
219.03 – 219.03 Mb
Chr 1:
74.19 – 74.19 Mb
PubMed search [1] [2]

Interleukin 8 receptor, alpha is a chemokine receptor. IL8RA is its human gene. IL8RA has also been designated CD181 (cluster of differentiation 181), and CXCR1. CXCR1 is now the IUPHAR Committee on Receptor Nomenclature and Drug Classification recommended name.

Function[edit]

The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein-activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, a gene encoding another high affinity IL8 receptor, and IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36.[1] Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.[2]

Clinical significance[edit]

Blocking CXCR1 (e.g., with repertaxin[3]) inhibits some human breast cancer stem cells (in vitro and in mice).[4]

CXCR1 can be cleaved and inactivated by Neutrophil Derived Serine Proteases (NSPs), leading to neutrophil dysfunction and impaired bacterial killing in Cystic Fibrosis lung disease.[5]

Interactions[edit]

Interleukin 8 receptor, alpha has been shown to interact with GNAI2.[6][7]

See also[edit]

References[edit]

  1. ^ "Entrez Gene: IL8RA interleukin 8 receptor, alpha". 
  2. ^ Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, Condron C, Chotirmall SH, Clynes M, O'Neill SJ, McElvaney NG (December 2010). "α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8". J. Clin. Invest. 120 (12): 4236–50. doi:10.1172/JCI41196. PMC 2993580. PMID 21060150. 
  3. ^ Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, Cavalieri B, Strippoli R, Cervellera MN, Di Bitondo R, Ferretti E, Mainiero F, Bizzarri C, Colotta F, Bertini R (February 2005). "Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2". Biochem. Pharmacol. 69 (3): 385–94. doi:10.1016/j.bcp.2004.10.007. PMID 15652230. 
  4. ^ Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS (February 2010). "CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts". J. Clin. Invest. 120 (2): 485–97. doi:10.1172/JCI39397. PMC 2810075. PMID 20051626. Lay summaryGenetic Engineering & Biotechnology News. 
  5. ^ Hartl D, Latzin P, Hordijk P, Marcos V, Rudolph C, Woischnik M, Krauss-Etschmann S, Koller B, Reinhardt D, Roscher AA, Roos D, Griese M (December 2007). "Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease". Nat. Med. 13 (12): 1423–30. doi:10.1038/nm1690. PMID 18059279. 
  6. ^ Damaj BB, McColl SR, Neote K, Songqing N, Ogborn KT, Hébert CA, Naccache PH (October 1996). "Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops". FASEB J. 10 (12): 1426–34. PMID 8903513. 
  7. ^ Damaj BB, McColl SR, Mahana W, Crouch MF, Naccache PH (May 1996). "Physical association of Gi2alpha with interleukin-8 receptors". J. Biol. Chem. 271 (22): 12783–9. doi:10.1074/jbc.271.22.12783. PMID 8662698. 

External links[edit]

Further_reading[edit]

  • Ahuja SK, Ozçelik T, Milatovitch A et al. (1993). "Molecular evolution of the human interleukin-8 receptor gene cluster". Nat. Genet. 2 (1): 31–6. doi:10.1038/ng0992-31. PMID 1303245. 
  • Lee J, Horuk R, Rice GC et al. (1992). "Characterization of two high affinity human interleukin-8 receptors". J. Biol. Chem. 267 (23): 16283–7. PMID 1379593. 
  • Morris SW, Nelson N, Valentine MB et al. (1992). "Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35". Genomics 14 (3): 685–91. doi:10.1016/S0888-7543(05)80169-7. PMID 1427896. 
  • Holmes WE, Lee J, Kuang WJ et al. (1991). "Structure and functional expression of a human interleukin-8 receptor". Science 253 (5025): 1278–80. doi:10.1126/science.1840701. PMID 1840701. 
  • Chuntharapai A, Lee J, Hébert CA, Kim KJ (1995). "Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes". J. Immunol. 153 (12): 5682–8. PMID 7527448. 
  • Chuntharapai A, Kim KJ (1995). "Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor". J. Immunol. 155 (5): 2587–94. PMID 7650389. 
  • Morohashi H, Miyawaki T, Nomura H et al. (1995). "Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells". J. Leukoc. Biol. 57 (1): 180–7. PMID 7829970. 
  • Schönbeck U, Brandt E, Petersen F et al. (1995). "IL-8 specifically binds to endothelial but not to smooth muscle cells". J. Immunol. 154 (5): 2375–83. PMID 7868904. 
  • Ahuja SK, Shetty A, Tiffany HL, Murphy PM (1994). "Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B". J. Biol. Chem. 269 (42): 26381–9. PMID 7929358. 
  • Sprenger H, Lloyd AR, Meyer RG et al. (1994). "Genomic structure, characterization, and identification of the promoter of the human IL-8 receptor A gene". J. Immunol. 153 (6): 2524–32. PMID 8077663. 
  • Schnitzel W, Monschein U, Besemer J (1994). "Monomer-dimer equilibria of interleukin-8 and neutrophil-activating peptide 2. Evidence for IL-8 binding as a dimer and oligomer to IL-8 receptor B". J. Leukoc. Biol. 55 (6): 763–70. PMID 8195702. 
  • Wu D, LaRosa GJ, Simon MI (1993). "G protein-coupled signal transduction pathways for interleukin-8". Science 261 (5117): 101–3. doi:10.1126/science.8316840. PMID 8316840. 
  • Sebok K, Woodside D, al-Aoukaty A et al. (1993). "IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (Go) protein". J. Immunol. 150 (4): 1524–34. PMID 8381837. 
  • Cerretti DP, Kozlosky CJ, Vanden Bos T et al. (1993). "Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2". Mol. Immunol. 30 (4): 359–67. doi:10.1016/0161-5890(93)90065-J. PMID 8384312. 
  • Mollereau C, Muscatelli F, Mattei MG et al. (1993). "The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor". Genomics 16 (1): 248–51. doi:10.1006/geno.1993.1167. PMID 8486366. 
  • Lloyd A, Modi W, Sprenger H et al. (1993). "Assignment of genes for interleukin-8 receptors (IL8R) A and B to human chromosome band 2q35". Cytogenet. Cell Genet. 63 (4): 238–40. doi:10.1159/000133541. PMID 8500355. 
  • Damaj BB, McColl SR, Mahana W et al. (1996). "Physical association of Gi2alpha with interleukin-8 receptors". J. Biol. Chem. 271 (22): 12783–9. doi:10.1074/jbc.271.22.12783. PMID 8662698. 
  • Ahuja SK, Murphy PM (1996). "The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor". J. Biol. Chem. 271 (34): 20545–50. doi:10.1074/jbc.271.34.20545. PMID 8702798. 
  • Damaj BB, McColl SR, Neote K et al. (1996). "Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops". FASEB J. 10 (12): 1426–34. PMID 8903513. 
  • Jerva LF, Sullivan G, Lolis E (1997). "Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: sequence analysis and mutagenesis identify receptor binding epitopes". Protein Sci. 6 (8): 1643–52. doi:10.1002/pro.5560060805. PMC 2143775. PMID 9260277. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.