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Chemokine (C-X-C motif) receptor 4
Identifiers
Symbols CXCR4; NPYR; CD184; D2S201E; FB22; HM89; HSY3RR; LAP3; LCR1; LESTR; NPY3R; NPYRL; NPYY3R; WHIM
External IDs OMIM162643 MGI109563 HomoloGene20739 IUPHAR: CXCR4 GeneCards: CXCR4 Gene
RNA expression pattern
PBB GE CXCR4 217028 at tn.png
PBB GE CXCR4 209201 x at tn.png
PBB GE CXCR4 211919 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7852 12767
Ensembl ENSG00000121966 ENSMUSG00000045382
UniProt P61073 A1E2I3
RefSeq (mRNA) NM_001008540 NM_009911
RefSeq (protein) NP_001008540 NP_034041
Location (UCSC) Chr 2:
136.59 - 136.59 Mb
Chr 1:
130.42 - 130.42 Mb
PubMed search [1] [2]

CXCR4, (a CXC chemokine Receptor), also called fusin, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is one of several chemokine receptors that HIV isolates can use to infect CD4+ T cells. Traditionally, HIV isolates that use CXCR4 are known as T-cell tropic isolates. Typically these viruses are found late in infection. It is unclear whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.

CXCR4 is upregulated during the implantation window in natural and Hormone Replacement Therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.

CXCR4's ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. Unusually for chemokines, SDF-1 and CXCR4 are a relatively "monogamous" ligand-receptor pair (other chemokines tend to use several different chemokine receptors in a fairly "promiscuous" manner). Because the interaction between SDF-1 and CXCR4 plays an important role in holding hematopoietic stem cells in the bone marrow, drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. Peripheral blood stem cell mobilization is very important in hematopoietic stem cell transplantation (as a recent alternative to transplantation of surgically-harvested bone marrow) and is currently performed using drugs such as G-CSF. G-CSF is a growth factor for neutrophils (a common type of white blood cells), and may act by increasing the activity of neutrophil-derived proteases such as neutrophil elastase in the bone marrow leading to proteolytic degradation of SDF-1. Plerixafor (AMD3100) is a drug, not yet in routine clinical use, which directly blocks the CXCR4 receptor. It is a very efficient inducer of hematopoietic stem cell mobilization in animal and human studies.

Contents

Interactions

CXCR4 has been shown to interact with USP14.[1]

See also

References

  1. ^ Mines, Marjelo A; Goodwin J Shawn, Limbird Lee E, Cui Fei-Fei, Fan Guo-Huang (Feb. 2009). "Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation". J. Biol. Chem. (United States) 284 (9): 5742–52. doi:10.1074/jbc.M808507200. ISSN 0021-9258. PMID 19106094.  

External links

Further reading

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  • Broder CC, Dimitrov DS (1997). "HIV and the 7-transmembrane domain receptors.". Pathobiology 64 (4): 171–9. doi:10.1159/000164032. PMID 9031325.  
  • Choe H, Martin KA, Farzan M, et al. (1998). "Structural interactions between chemokine receptors, gp120 Env and CD4.". Semin. Immunol. 10 (3): 249–57. doi:10.1006/smim.1998.0127. PMID 9653051.  
  • Freedman BD, Liu QH, Del Corno M, Collman RG (2004). "HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages.". Immunol. Res. 27 (2-3): 261–76. doi:10.1385/IR:27:2-3:261. PMID 12857973.  
  • Esté JA (2004). "Virus entry as a target for anti-HIV intervention.". Curr. Med. Chem. 10 (17): 1617–32. doi:10.2174/0929867033457098. PMID 12871111.  
  • Gallo SA, Finnegan CM, Viard M, et al. (2003). "The HIV Env-mediated fusion reaction.". Biochim. Biophys. Acta 1614 (1): 36–50. doi:10.1016/S0005-2736(03)00161-5. PMID 12873764.  
  • Zaitseva M, Peden K, Golding H (2003). "HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral-cell fusion and as targets for entry inhibitors.". Biochim. Biophys. Acta 1614 (1): 51–61. doi:10.1016/S0005-2736(03)00162-7. PMID 12873765.  
  • Lee C, Liu QH, Tomkowicz B, et al. (2004). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways.". J. Leukoc. Biol. 74 (5): 676–82. doi:10.1189/jlb.0503206. PMID 12960231.  
  • Yi Y, Lee C, Liu QH, et al. (2004). "Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: Implications for neuropathogenesis.". J. Neurovirol. 10 Suppl 1: 91–6. PMID 14982745.  
  • Seibert C, Sakmar TP (2004). "Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs.". Curr. Pharm. Des. 10 (17): 2041–62. doi:10.2174/1381612043384312. PMID 15279544.  
  • Perfettini JL, Castedo M, Roumier T, et al. (2006). "Mechanisms of apoptosis induction by the HIV-1 envelope.". Cell Death Differ. 12 Suppl 1: 916–23. doi:10.1038/sj.cdd.4401584. PMID 15719026.  
  • King JE, Eugenin EA, Buckner CM, Berman JW (2006). "HIV tat and neurotoxicity.". Microbes Infect. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.  
  • Kryczek I, Wei S, Keller E, et al. (2007). "Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis.". Am. J. Physiol., Cell Physiol. 292 (3): C987–95. doi:10.1152/ajpcell.00406.2006. PMID 16943240.  
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  • Grange JM (1980). "Tuberculosis: the changing tubercle.". British journal of hospital medicine 22 (6): 540–8. PMID 118789.  
  • Nomura H, Nielsen BW, Matsushima K (1994). "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors.". Int. Immunol. 5 (10): 1239–49. doi:10.1093/intimm/5.10.1239. PMID 7505609.  
  • Lu ZH, Wang ZX, Horuk R, et al. (1995). "The promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines is primarily localized to sequences in the amino-terminal domain.". J. Biol. Chem. 270 (44): 26239–45. doi:10.1074/jbc.270.44.26239. PMID 7592830.  
  • Jazin EE, Yoo H, Blomqvist AG, et al. (1993). "A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells.". Regul. Pept. 47 (3): 247–58. doi:10.1016/0167-0115(93)90392-L. PMID 8234909.  
  • Loetscher M, Geiser T, O'Reilly T, et al. (1994). "Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes.". J. Biol. Chem. 269 (1): 232–7. PMID 8276799.  
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