Receptor de interleucina 8, alfa


PDB 1ilp
Receptor (motivo C-X-C) 1 de quimiocinas (Chemokine (C-X-C motif) receptor 1)
Identificadores
Símbolo	CXCR1 ; C-C; C-C-CKR-1; CD128; CD181; CDw128a; CKR-1; CMKAR1; IL8R1; IL8RA; IL8RBA
Entrez	3577
HUGO	6026
OMIM	146929
RefSeq	NP_000625
UniProt	P25024
Outros datos
Locus	Cr. 2 :(219.03 – 219.03 Mb)

O receptor de interleucina 8, alfa (IL8RA) é un receptor de quimiocinas. O seu xene humano é IL8RA. O IL8RA tamén foi designado como CD181 e CXCR1. CXCR1 é agora o nome recomendado polo Comité sobre Nomenclatura de Receptores e Clasificación de Fármacos da IUPHAR.

Función

A proteína codificada por este xene é membro da familia do receptor acoplado á proteína G. Esta proteína é un receptor da interleucina 8 (IL8). Únese a IL8 con alta afinidade, e transduce o sinal a través dun sistema de segundo mensaxeiro activado pola proteína G. Os estudos knockout en ratos indican que esta proteína inhibe a migración dos precursores dos oligodendrocitos embrionaria na medula espiñal en desenvolvemento. O xene IL8RA, xunto con IL8RB, que codifica outro receptor de alta afinidade de IL8, e IL8RBP, que é un pseudoxene de IL8RB, forman un cluster de xenes na rexión do cromosoma 2 q33-q36. Existen variantes de splicing.^[1] A estimulación de CXCR1 en neutrófilos polo seu ligando primario a interleucina 8, causa a activación e quimiotaxe dos neutrófilos.^[2]

Importancia clínica

O bloqueo de CXCR1 (por exemplo con repertaxina^[3]) inhibe algunhas células nai de cancro de mama humano (in vitro e en ratos).^[4]

O CXCR1 pode ser clivado e inactivado por serina proteases derivadas de neutrófilo (NSPs), o que orixina a disfunción de neutrófilos e altera a morte de bacterias na enfermidade pulmonar da fibrose quística.^[5]

Interaccións

O receptor de interleucina 8, alfa presenta interaccións con GNAI2.^[6]^[7]

Notas

↑ "Entrez Gene: IL8RA interleukin 8 receptor, alpha".
↑ 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". J. Clin. Invest. 120 (12): 4236–50. PMC 2993580. PMID 21060150. doi:10.1172/JCI41196.
↑ 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. PMID 15652230. doi:10.1016/j.bcp.2004.10.007.
↑ 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. PMC 2810075. PMID 20051626. doi:10.1172/JCI39397. Resumo divulgativo – Genetic Engineering & Biotechnology News.
↑ 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. PMID 18059279. doi:10.1038/nm1690.
↑ 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. PMID 8903513.
↑ 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. PMID 8662698. doi:10.1074/jbc.271.22.12783.

Véxase tamén

Outros artigos

Ligazóns externas

"Chemokine Receptors: CXCR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arquivado dende o orixinal o 03 de marzo de 2016.

Bibliografía

Ahuja SK, Ozçelik T, Milatovitch A, Francke U, Murphy PM (1992). "Molecular evolution of the human interleukin-8 receptor gene cluster". Nat. Genet. 2 (1): 31–6. PMID 1303245. doi:10.1038/ng0992-31.
Lee J, Horuk R, Rice GC, Bennett GL, Camerato T, Wood WI (1992). "Characterization of two high affinity human interleukin-8 receptors". J. Biol. Chem. 267 (23): 16283–7. PMID 1379593.
Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP (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. PMID 1427896. doi:10.1016/S0888-7543(05)80169-7.
Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI (1991). "Structure and functional expression of a human interleukin-8 receptor". Science 253 (5025): 1278–80. PMID 1840701. doi:10.1126/science.1840701.
Chuntharapai A, Lee J, Hébert CA, Kim KJ (1994). "Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes". J. Immunol. 153 (12): 5682–8. PMID 7527448.
Chuntharapai A, Kim KJ (1995). "Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor". J. Immunol. 155 (5): 2587–94. PMID 7650389.
Morohashi H, Miyawaki T, Nomura H, Kuno K, Murakami S, Matsushima K, Mukaida N (1995). "Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells". J. Leukoc. Biol. 57 (1): 180–7. PMID 7829970.
Schönbeck U, Brandt E, Petersen F, Flad HD, Loppnow H (1995). "IL-8 specifically binds to endothelial but not to smooth muscle cells". J. Immunol. 154 (5): 2375–83. PMID 7868904.
Ahuja SK, Shetty A, Tiffany HL, Murphy PM (1994). "Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B". J. Biol. Chem. 269 (42): 26381–9. PMID 7929358.
Sprenger H, Lloyd AR, Meyer RG, Johnston JA, Kelvin DJ (1994). "Genomic structure, characterization, and identification of the promoter of the human IL-8 receptor A gene". J. Immunol. 153 (6): 2524–32. PMID 8077663.
Schnitzel W, Monschein U, Besemer J (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". J. Leukoc. Biol. 55 (6): 763–70. PMID 8195702.
Wu D, LaRosa GJ, Simon MI (1993). "G protein-coupled signal transduction pathways for interleukin-8". Science 261 (5117): 101–3. PMID 8316840. doi:10.1126/science.8316840.
Sebok K, Woodside D, al-Aoukaty A, Ho AD, Gluck S, Maghazachi AA (1993). "IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (Go) protein". J. Immunol. 150 (4): 1524–34. PMID 8381837.
Cerretti DP, Kozlosky CJ, Vanden Bos T, Nelson N, Gearing DP, Beckmann MP (1993). "Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2". Mol. Immunol. 30 (4): 359–67. PMID 8384312. doi:10.1016/0161-5890(93)90065-J.
Mollereau C, Muscatelli F, Mattei MG, Vassart G, Parmentier M (1993). "The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor". Genomics 16 (1): 248–51. PMID 8486366. doi:10.1006/geno.1993.1167.
Lloyd A, Modi W, Sprenger H, Cevario S, Oppenheim J, Kelvin D (1993). "Assignment of genes for interleukin-8 receptors (IL8R) A and B to human chromosome band 2q35". Cytogenet. Cell Genet. 63 (4): 238–40. PMID 8500355. doi:10.1159/000133541.
Damaj BB, McColl SR, Mahana W, Crouch MF, Naccache PH (1996). "Physical association of Gi2alpha with interleukin-8 receptors". J. Biol. Chem. 271 (22): 12783–9. PMID 8662698. doi:10.1074/jbc.271.22.12783.
Ahuja SK, Murphy PM (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". J. Biol. Chem. 271 (34): 20545–50. PMID 8702798. doi:10.1074/jbc.271.34.20545.
Damaj BB, McColl SR, Neote K, Songqing N, Ogborn KT, Hébert CA, Naccache PH (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. PMID 8903513.
Jerva LF, Sullivan G, Lolis E (1997). "Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: sequence analysis and mutagenesis identify receptor binding epitopes". Protein Sci. 6 (8): 1643–52. PMC 2143775. PMID 9260277. doi:10.1002/pro.5560060805.

[entrez-1] "Entrez Gene: IL8RA interleukin 8 receptor, alpha".

[pmid21060150-2] 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". J. Clin. Invest. 120 (12): 4236–50. PMC 2993580. PMID 21060150. doi:10.1172/JCI41196.

[pmid15652230-3] 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. PMID 15652230. doi:10.1016/j.bcp.2004.10.007.

[pmid20051626-4] 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. PMC 2810075. PMID 20051626. doi:10.1172/JCI39397. Resumo divulgativo – Genetic Engineering & Biotechnology News.

[pmid18059279-5] 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. PMID 18059279. doi:10.1038/nm1690.

[pmid8903513-6] 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. PMID 8903513.

[pmid8662698-7] 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. PMID 8662698. doi:10.1074/jbc.271.22.12783.

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