Interleukin 8 receptor, beta explained

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

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 (G_i/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.

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. IL8RB, IL8RA, which encodes 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

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

• Interleukin 8 receptor, alpha
• Interleukin 8
• Interleukin
• Interleukin receptor
• Cluster of differentiation
• G protein-coupled receptor

Further reading

• Brandt E, Ludwig A, Petersen F, Flad HD . Platelet-derived CXC chemokines: old players in new games . Immunological Reviews . 177 . 204–16 . Oct 2000 . 11138777 . 10.1034/j.1600-065X.2000.17705.x . 46515022 .
• Robertson MJ . Role of chemokines in the biology of natural killer cells . Journal of Leukocyte Biology . 71 . 2 . 173–83 . Feb 2002 . 10.1189/jlb.71.2.173 . 11818437 . 720060 .
• Ahuja SK, Ozçelik T, Milatovitch A, Francke U, Murphy PM . Molecular evolution of the human interleukin-8 receptor gene cluster . Nature Genetics . 2 . 1 . 31–6 . Sep 1992 . 1303245 . 10.1038/ng0992-31 . 19732372 .
• Lee J, Horuk R, Rice GC, Bennett GL, Camerato T, Wood WI . Characterization of two high affinity human interleukin-8 receptors . The Journal of Biological Chemistry . 267 . 23 . 16283–7 . Aug 1992 . 10.1016/S0021-9258(18)41997-7 . 1379593 . free .
• Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP . 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 . Nov 1992 . 1427896 . 10.1016/S0888-7543(05)80169-7 .
• Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI . Structure and functional expression of a human interleukin-8 receptor . Science . 253 . 5025 . 1278–80 . Sep 1991 . 1840701 . 10.1126/science.1840701 . 1991Sci...253.1278H .
• Murphy PM, Tiffany HL . Cloning of complementary DNA encoding a functional human interleukin-8 receptor . Science . 253 . 5025 . 1280–3 . Sep 1991 . 1891716 . 10.1126/science.1891716 . 1991Sci...253.1280M .
• Sprenger H, Lloyd AR, Lautens LL, Bonner TI, Kelvin DJ . Structure, genomic organization, and expression of the human interleukin-8 receptor B gene . The Journal of Biological Chemistry . 269 . 15 . 11065–72 . Apr 1994 . 10.1016/S0021-9258(19)78092-2 . 7512557 . free .
• Morohashi H, Miyawaki T, Nomura H, Kuno K, Murakami S, Matsushima K, Mukaida N . 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 . Jan 1995 . 7829970 . 10.1002/jlb.57.1.180. 7819367 .
• Ahuja SK, Shetty A, Tiffany HL, Murphy PM . 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 . Oct 1994 . 10.1016/S0021-9258(18)47205-5 . 7929358 . free .
• Cacalano G, Lee J, Kikly K, Ryan AM, Pitts-Meek S, Hultgren B, Wood WI, Moore MW . Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog . Science . 265 . 5172 . 682–4 . Jul 1994 . 8036519 . 10.1126/science.8036519 . 1994Sci...265..682C .
• Harada A, Kuno K, Nomura H, Mukaida N, Murakami S, Matsushima K . Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor . Gene . 142 . 2 . 297–300 . May 1994 . 8194768 . 10.1016/0378-1119(94)90278-X .
• Schnitzel W, Monschein U, Besemer J . 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 . Jun 1994 . 8195702 . 10.1002/jlb.55.6.763. 5948202 .
• Mueller SG, Schraw WP, Richmond A . 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 . Jan 1994 . 10.1016/S0021-9258(17)42123-5 . 8294449 . free .
• Wu D, LaRosa GJ, Simon MI . G protein-coupled signal transduction pathways for interleukin-8 . Science . 261 . 5117 . 101–3 . Jul 1993 . 8316840 . 10.1126/science.8316840 . 1993Sci...261..101W .
• Cerretti DP, Kozlosky CJ, Vanden Bos T, Nelson N, Gearing DP, Beckmann MP . Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2 . Molecular Immunology . 30 . 4 . 359–67 . Mar 1993 . 8384312 . 10.1016/0161-5890(93)90065-J .
• Ahuja SK, Lee JC, Murphy PM . 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 . Jan 1996 . 8550564 . 10.1074/jbc.271.1.225 . free .
• Hammond ME, Shyamala V, Siani MA, Gallegos CA, Feucht PH, Abbott J, Lapointe GR, Moghadam M, Khoja H, Zakel J, Tekamp-Olson P . 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 . Apr 1996 . 8626516 . 10.1074/jbc.271.14.8228 . free .
• Damaj BB, McColl SR, Mahana W, Crouch MF, Naccache PH . Physical association of Gi2alpha with interleukin-8 receptors . The Journal of Biological Chemistry . 271 . 22 . 12783–9 . May 1996 . 8662698 . 10.1074/jbc.271.22.12783 . free .
• Ahuja SK, Murphy PM . 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 . Aug 1996 . 8702798 . 10.1074/jbc.271.34.20545 . free .

External links

• • Web site: Chemokine Receptors: CXCR2 . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-03 . 2015-06-15 . https://web.archive.org/web/20150615052358/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2212 . dead .

Notes and References

1. Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP . 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 . Nov 1992 . 1427896 . 10.1016/S0888-7543(05)80169-7 .
2. Web site: Entry in: gpDB, database of GPCRs, G-proteins, Effectors and their interactions. 3 October 2012.
3. Web site: 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 . Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits . Nature Genetics . 46 . 6 . 629–34 . Jun 2014 . 24777453 . 4050975 . 10.1038/ng.2962 .
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 . Chemokine signaling via the CXCR2 receptor reinforces senescence . Cell . 133 . 6 . 1006–18 . Jun 2008 . 18555777 . 10.1016/j.cell.2008.03.038 . 6708172 . free .