Interleukin 8 receptor, alpha

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CXCR1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCXCR1, C-C, C-C-CKR-1, CD128, CD181, CDw128a, CKR-1, CMKAR1, IL8R1, IL8RA, IL8RBA, Interleukin 8 receptor, C-X-C motif chemokine receptor 1
External IDsOMIM: 146929 MGI: 2448715 HomoloGene: 68074 GeneCards: CXCR1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000634

NM_178241

RefSeq (protein)

NP_000625

NP_839972

Location (UCSC)Chr 2: 218.16 – 218.17 MbChr 1: 74.23 – 74.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD181 (cluster of differentiation 181). The IUPHAR Committee on Receptor Nomenclature and Drug Classification use the HGNC recommended name, CXCR1.

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. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. IL8RA, IL8RB, 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.[5] Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.[6]

Clinical significance

Blocking CXCR1 (e.g., with repertaxin[7]) inhibits some human breast cancer stem cells (in vitro and in mice).[8]

In malignant melanoma expression of CXCR1 at the cell surface is present, independent of the cancers stage. It is thought to have a role in the cell growth and angiogenesis required for tumour survival. In this way it has been identified as a potential therapeutic target.[9]

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.[10]

Interactions

Interleukin 8 receptor, alpha has been shown to interact with GNAI2.[11][12]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163464 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048480 - 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. ^ "Entrez Gene: IL8RA interleukin 8 receptor, alpha".
  6. ^ 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" (PDF). J. Clin. Invest. 120 (12): 4236–50. doi:10.1172/JCI41196. PMC 2993580. PMID 21060150.
  7. ^ 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.
  8. ^ 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.
  9. ^ Sharma, Bhawna; Singh, Seema; Varney, Michelle L; Singh, Rakesh K (2010-04-01). "Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma". Expert Opinion on Therapeutic Targets. 14 (4): 435–442. doi:10.1517/14728221003652471. ISSN 1472-8222. PMC 4229031. PMID 20230195.
  10. ^ 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. S2CID 9594986.
  11. ^ 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. doi:10.1096/fasebj.10.12.8903513. PMID 8903513. S2CID 9744575.
  12. ^ 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.

Further reading

External links

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