Interleukin 8 receptor, beta

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.^[5]

CXCR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4Q3H
Identifiers
Aliases	CXCR2, CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB, Interleukin 8 receptor, beta, C-X-C motif chemokine receptor 2, WHIMS2
External IDs	OMIM: 146928; MGI: 105303; HomoloGene: 10439; GeneCards: CXCR2; OMA:CXCR2 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q35 Start 218,125,289 bp[1] End 218,137,251 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C3|1 38.41 cM Start 74,193,148 bp[2] End 74,200,405 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood periodontal fiber granulocyte trabecular bone epithelium of esophagus monocyte gonad spleen oral cavity bone marrow Top expressed in granulocyte placenta bone marrow esophagus embryo spleen embryo blastocyst lip lung More reference expression data BioGPS More reference expression data
Gene ontology Molecular function C-X-C chemokine receptor activity interleukin-8 binding protein binding interleukin-8 receptor activity chemokine receptor activity signal transducer activity G protein-coupled receptor activity C-C chemokine receptor activity chemokine binding C-C chemokine binding Cellular component integral component of membrane membrane mast cell granule plasma membrane integral component of plasma membrane intracellular anatomical structure cell surface secretory granule membrane external side of plasma membrane Biological process neutrophil activation receptor internalization dendritic cell chemotaxis chemotaxis cellular defense response phospholipase C-activating G protein-coupled receptor signaling pathway cell surface receptor signaling pathway positive regulation of cell population proliferation inflammatory response chemokine-mediated signaling pathway neutrophil degranulation G protein-coupled receptor signaling pathway acute inflammatory response to antigenic stimulus positive regulation of leukocyte chemotaxis positive regulation of cytosolic calcium ion concentration positive regulation of cardiac muscle cell apoptotic process neutrophil chemotaxis midbrain development negative regulation of neutrophil apoptotic process negative regulation of apoptotic process positive regulation of vascular permeability positive regulation of angiogenesis metanephric tubule morphogenesis positive regulation of neutrophil chemotaxis signal transduction interleukin-8-mediated signaling pathway immune response calcium-mediated signaling cell chemotaxis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3579 12765 Ensembl ENSG00000180871 ENSMUSG00000026180 UniProt P25025 P35343 RefSeq (mRNA) NM_001168298 NM_001557 NM_009909 RefSeq (protein) NP_001161770 NP_001548 NP_034039 Location (UCSC) Chr 2: 218.13 – 218.14 Mb Chr 1: 74.19 – 74.2 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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^[6]). 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.^[7]

Mutations in CXCR2 cause hematological traits.^[8]

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.^[9]

See also

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

References

1. GRCh38: Ensembl release 89: ENSG00000180871 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026180 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entry in: gpDB, database of GPCRs, G-proteins, Effectors and their interactions". Retrieved 3 October 2012.
7. "Entrez Gene: IL8RB interleukin 8 receptor, beta".
8. 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. PMC 4050975. PMID 24777453.
9. 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. S2CID 6708172.

Further reading

• 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. S2CID 46515022.
• Robertson MJ (Feb 2002). "Role of chemokines in the biology of natural killer cells". Journal of Leukocyte Biology. 71 (2): 173–83. doi:10.1189/jlb.71.2.173. PMID 11818437. S2CID 720060.
• 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. S2CID 19732372.
• 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. doi:10.1016/S0021-9258(18)41997-7. 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. Bibcode:1991Sci...253.1278H. 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. Bibcode:1991Sci...253.1280M. 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. doi:10.1016/S0021-9258(19)78092-2. 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. doi:10.1002/jlb.57.1.180. PMID 7829970. S2CID 7819367.
• 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. doi:10.1016/S0021-9258(18)47205-5. 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. Bibcode:1994Sci...265..682C. 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. doi:10.1002/jlb.55.6.763. PMID 8195702. S2CID 5948202.
• 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. doi:10.1016/S0021-9258(17)42123-5. PMID 8294449.
• Wu D, LaRosa GJ, Simon MI (Jul 1993). "G protein-coupled signal transduction pathways for interleukin-8". Science. 261 (5117): 101–3. Bibcode:1993Sci...261..101W. 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

• CD182+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• "Chemokine Receptors: CXCR2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2015-06-15. Retrieved 2008-12-03.