Biology:Interleukin 8 receptor, alpha

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Short description: Mammalian protein found in Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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 This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1.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.[1] Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.[2]

Clinical significance

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

In 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.[5]

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.[6]

Interactions

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

See also

References

  1. ↑ "Entrez Gene: IL8RA interleukin 8 receptor, alpha". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3577. 
  2. ↑ "α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8". The Journal of Clinical Investigation 120 (12): 4236–4250. December 2010. doi:10.1172/JCI41196. PMID 21060150. 
  3. ↑ "Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2". Biochemical Pharmacology 69 (3): 385–394. February 2005. doi:10.1016/j.bcp.2004.10.007. PMID 15652230. 
  4. ↑ "CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts". The Journal of Clinical Investigation 120 (2): 485–497. February 2010. doi:10.1172/JCI39397. PMID 20051626. 
  5. ↑ "Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma". Expert Opinion on Therapeutic Targets 14 (4): 435–442. April 2010. doi:10.1517/14728221003652471. PMID 20230195. 
  6. ↑ "Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease". Nature Medicine 13 (12): 1423–1430. December 2007. doi:10.1038/nm1690. PMID 18059279. 
  7. ↑ "Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops". FASEB Journal 10 (12): 1426–1434. October 1996. doi:10.1096/fasebj.10.12.8903513. PMID 8903513. 
  8. ↑ "Physical association of Gi2alpha with interleukin-8 receptors". The Journal of Biological Chemistry 271 (22): 12783–12789. May 1996. doi:10.1074/jbc.271.22.12783. PMID 8662698. 

Further reading

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



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