Interleukin 8 receptor, beta

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Chemokine (C-X-C motif) receptor 2
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CXCR2 ; CD182; CDw128b; CMKAR2; IL8R2; IL8RA; IL8RB
External IDs OMIM146928 MGI105303 HomoloGene10439 IUPHAR: 69 ChEMBL: 2434 GeneCards: CXCR2 Gene
RNA expression pattern
PBB GE IL8RB 207008 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3579 12765
Ensembl ENSG00000180871 ENSMUSG00000026180
UniProt P25025 P35343
RefSeq (mRNA) NM_001168298 NM_009909
RefSeq (protein) NP_001161770 NP_034039
Location (UCSC) Chr 2:
218.13 – 218.14 Mb
Chr 1:
74.15 – 74.16 Mb
PubMed search [1] [2]

Interleukin 8 receptor, beta is a chemokine receptor. IL8RB is also known as CXCR2, and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name.[1]

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 (Gi/o-coupled[2]). This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. In addition, it binds ligands CXCL2, CXCL3, and CXCL5.

This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, 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.[3]

Mutations in CXCR2 cause hematological traits .[4]

Senescence[edit]

Knock-down studies involving the chemokine receptor CXCR2 alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Also, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism.[5]

See also[edit]

References[edit]

  1. ^ Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP (Nov 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. 
  2. ^ "Entry in: gpDB, database of GPCRs, G-proteins, Effectors and their interactions". Retrieved 3 October 2012. 
  3. ^ "Entrez Gene: IL8RB interleukin 8 receptor, beta". 
  4. ^ Auer PL, Teumer A, Schick U, O'Shaughnessy A, Lo KS, Chami N, Carlson C, de Denus S, Dubé MP, Haessler J, Jackson RD, Kooperberg C, Perreault LP, Nauck M, Peters U, Rioux JD, Schmidt F, Turcot V, Völker U, Völzke H, Greinacher A, Hsu L, Tardif JC, Diaz GA, Reiner AP, Lettre G (Jun 2014). "Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits". Nature Genetics 46 (6): 629–34. doi:10.1038/ng.2962. PMID 24777453. 
  5. ^ Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E, Gil J (Jun 2008). "Chemokine signaling via the CXCR2 receptor reinforces senescence". Cell 133 (6): 1006–18. doi:10.1016/j.cell.2008.03.038. PMID 18555777. 

Further reading[edit]

  • Brandt E, Ludwig A, Petersen F, Flad HD (Oct 2000). "Platelet-derived CXC chemokines: old players in new games". Immunological Reviews 177: 204–16. doi:10.1034/j.1600-065X.2000.17705.x. PMID 11138777. 
  • Robertson MJ (Feb 2002). "Role of chemokines in the biology of natural killer cells". Journal of Leukocyte Biology 71 (2): 173–83. PMID 11818437. 
  • Ahuja SK, Ozçelik T, Milatovitch A, Francke U, Murphy PM (Sep 1992). "Molecular evolution of the human interleukin-8 receptor gene cluster". Nature Genetics 2 (1): 31–6. doi:10.1038/ng0992-31. PMID 1303245. 
  • Lee J, Horuk R, Rice GC, Bennett GL, Camerato T, Wood WI (Aug 1992). "Characterization of two high affinity human interleukin-8 receptors". The Journal of Biological Chemistry 267 (23): 16283–7. PMID 1379593. 
  • Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP (Nov 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, Rice GC, Wood WI (Sep 1991). "Structure and functional expression of a human interleukin-8 receptor". Science 253 (5025): 1278–80. doi:10.1126/science.1840701. PMID 1840701. 
  • Murphy PM, Tiffany HL (Sep 1991). "Cloning of complementary DNA encoding a functional human interleukin-8 receptor". Science 253 (5025): 1280–3. doi:10.1126/science.1891716. PMID 1891716. 
  • Sprenger H, Lloyd AR, Lautens LL, Bonner TI, Kelvin DJ (Apr 1994). "Structure, genomic organization, and expression of the human interleukin-8 receptor B gene". The Journal of Biological Chemistry 269 (15): 11065–72. PMID 7512557. 
  • Morohashi H, Miyawaki T, Nomura H, Kuno K, Murakami S, Matsushima K, Mukaida N (Jan 1995). "Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells". Journal of Leukocyte Biology 57 (1): 180–7. PMID 7829970. 
  • Ahuja SK, Shetty A, Tiffany HL, Murphy PM (Oct 1994). "Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B". The Journal of Biological Chemistry 269 (42): 26381–9. PMID 7929358. 
  • Cacalano G, Lee J, Kikly K, Ryan AM, Pitts-Meek S, Hultgren B, Wood WI, Moore MW (Jul 1994). "Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog". Science 265 (5172): 682–4. doi:10.1126/science.8036519. PMID 8036519. 
  • Harada A, Kuno K, Nomura H, Mukaida N, Murakami S, Matsushima K (May 1994). "Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor". Gene 142 (2): 297–300. doi:10.1016/0378-1119(94)90278-X. PMID 8194768. 
  • Schnitzel W, Monschein U, Besemer J (Jun 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". Journal of Leukocyte Biology 55 (6): 763–70. PMID 8195702. 
  • Mueller SG, Schraw WP, Richmond A (Jan 1994). "Melanoma growth stimulatory activity enhances the phosphorylation of the class II interleukin-8 receptor in non-hematopoietic cells". The Journal of Biological Chemistry 269 (3): 1973–80. PMID 8294449. 
  • Wu D, LaRosa GJ, Simon MI (Jul 1993). "G protein-coupled signal transduction pathways for interleukin-8". Science 261 (5117): 101–3. doi:10.1126/science.8316840. PMID 8316840. 
  • Cerretti DP, Kozlosky CJ, Vanden Bos T, Nelson N, Gearing DP, Beckmann MP (Mar 1993). "Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2". Molecular Immunology 30 (4): 359–67. doi:10.1016/0161-5890(93)90065-J. PMID 8384312. 
  • Ahuja SK, Lee JC, Murphy PM (Jan 1996). "CXC chemokines bind to unique sets of selectivity determinants that can function independently and are broadly distributed on multiple domains of human interleukin-8 receptor B. Determinants of high affinity binding and receptor activation are distinct". The Journal of Biological Chemistry 271 (1): 225–32. doi:10.1074/jbc.271.1.225. PMID 8550564. 
  • Hammond ME, Shyamala V, Siani MA, Gallegos CA, Feucht PH, Abbott J, Lapointe GR, Moghadam M, Khoja H, Zakel J, Tekamp-Olson P (Apr 1996). "Receptor recognition and specificity of interleukin-8 is determined by residues that cluster near a surface-accessible hydrophobic pocket". The Journal of Biological Chemistry 271 (14): 8228–35. doi:10.1074/jbc.271.14.8228. PMID 8626516. 
  • Damaj BB, McColl SR, Mahana W, Crouch MF, Naccache PH (May 1996). "Physical association of Gi2alpha with interleukin-8 receptors". The Journal of Biological Chemistry 271 (22): 12783–9. doi:10.1074/jbc.271.22.12783. PMID 8662698. 
  • Ahuja SK, Murphy PM (Aug 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". The Journal of Biological Chemistry 271 (34): 20545–50. doi:10.1074/jbc.271.34.20545. PMID 8702798. 

External links[edit]