CXCR4
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Location (UCSC) | Chr 2: 136.11 – 136.12 Mb | Chr 1: 128.52 – 128.52 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a
Function
CXCR-4 is an alpha-
CXCR4 is
CXCR4's
CXCR4 is present in newly generated neurons during embryogenesis and adult life where it plays a role in neuronal guidance. The levels of the receptor decrease as neurons mature. CXCR4 mutant mice have aberrant neuronal distribution. This has been implicated in disorders such as epilepsy.[11]
CXCR4 dimerization is dynamic and increases with concentration.[12]
Clinical significance
Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as
It has been associated with
While CXCR4's expression is low or absent in many healthy tissues, it was demonstrated to be expressed in over 23 types of cancer, including breast cancer, ovarian cancer, melanoma, and prostate cancer. Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow.
Drug response
Chronic exposure to
Interactions
CXCR4 has been shown to
See also
- CXCR4 antagonist
- HIV tropism
- Entry inhibitor
- Discovery and development of CCR5 receptor antagonists
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000121966 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045382 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 36552134.
- S2CID 36571818.
- ^ "Gene group: C-X-C motif chemokine receptors (CXCR)". HUGO Gene Nomenclature Committee.
- PMID 20228059.
- S2CID 24072570.
- S2CID 23194228.
- PMID 12183377.
- PMID 33148803.
- S2CID 2543277.
- PMID 17533053.
- PMID 18274673.
- PMID 24366360.
- PMID 25853747.
- PMID 20839032.
- S2CID 205467365.
- PMID 19646861.
- PMID 21907922.
- PMID 21484257.
- PMID 19106094.
Further reading
- Wilkinson D (September 1996). "Cofactors provide the entry keys. HIV-1". Current Biology. 6 (9): 1051–3. S2CID 18710567.
- Broder CC, Dimitrov DS (1996). "HIV and the 7-transmembrane domain receptors". Pathobiology. 64 (4): 171–9. PMID 9031325.
- Choe H, Martin KA, Farzan M, Sodroski J, Gerard NP, Gerard C (June 1998). "Structural interactions between chemokine receptors, gp120 Env and CD4". Seminars in Immunology. 10 (3): 249–57. PMID 9653051.
- Freedman BD, Liu QH, Del Corno M, Collman RG (2003). "HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages". Immunologic Research. 27 (2–3): 261–76. S2CID 32006625.
- Esté JA (September 2003). "Virus entry as a target for anti-HIV intervention". Current Medicinal Chemistry. 10 (17): 1617–32. PMID 12871111.
- Gallo SA, Finnegan CM, Viard M, Raviv Y, Dimitrov A, Rawat SS, Puri A, Durell S, Blumenthal R (July 2003). "The HIV Env-mediated fusion reaction". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1614 (1): 36–50. PMID 12873764.
- Zaitseva M, Peden K, Golding H (July 2003). "HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral-cell fusion and as targets for entry inhibitors". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1614 (1): 51–61. PMID 12873765.
- Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG (November 2003). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways". Journal of Leukocyte Biology. 74 (5): 676–82. S2CID 11362623.
- Yi Y, Lee C, Liu QH, Freedman BD, Collman RG (2004). "Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: Implications for neuropathogenesis". Journal of Neurovirology. 10. 10 (Suppl 1): 91–6. S2CID 9065929.
- Seibert C, Sakmar TP (2004). "Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs". Current Pharmaceutical Design. 10 (17): 2041–62. PMID 15279544.
- Perfettini JL, Castedo M, Roumier T, Andreau K, Nardacci R, Piacentini M, Kroemer G (August 2005). "Mechanisms of apoptosis induction by the HIV-1 envelope". Cell Death and Differentiation. 12. 12 (Suppl 1): 916–23. PMID 15719026.
- King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection / Institut Pasteur. 8 (5): 1347–57. PMID 16697675.
- Kryczek I, Wei S, Keller E, Liu R, Zou W (March 2007). "Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis". American Journal of Physiology. Cell Physiology. 292 (3): C987-95. S2CID 7423893.
- Arya M, Ahmed H, Silhi N, Williamson M, Patel HR (2007). "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration". Tumour Biology. 28 (3): 123–31. S2CID 44356923.
- Grange JM (December 1979). "Tuberculosis: the changing tubercle". British Journal of Hospital Medicine. 22 (6): 540–8. PMID 118789.
- Nomura H, Nielsen BW, Matsushima K (October 1993). "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors". PMID 7505609.
- Lu ZH, Wang ZX, Horuk R, Hesselgesser J, Lou YC, Hadley TJ, Peiper SC (November 1995). "The promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines is primarily localized to sequences in the amino-terminal domain". The Journal of Biological Chemistry. 270 (44): 26239–45. PMID 7592830.
- Jazin EE, Yoo H, Blomqvist AG, Yee F, Weng G, Walker MW, Salon J, Larhammar D, Wahlestedt C (September 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". Regulatory Peptides. 47 (3): 247–58. S2CID 25271767.
- Loetscher M, Geiser T, O'Reilly T, Zwahlen R, Baggiolini M, Moser B (January 1994). "Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes". The Journal of Biological Chemistry. 269 (1): 232–7. PMID 8276799.
- Wang J, Liu X, Lu H, Jiang C, Cui X, Yu L, Fu X, Li Q, Wang J (March 2015). "CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs for protection after ischemic stroke in mice". Brain, Behavior, and Immunity. 45: 98–108. PMID 25526817.
- Federsppiel B, Melhado IG, Duncan AM, Delaney A, Schappert K, Clark-Lewis I, Jirik FR (June 1993). "Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen". Genomics. 16 (3): 707–12. PMID 8325644.
- Arimont A, Sun S, Smit MJ, Leurs R, de Esch IJ, de Graaf C (2017). "Structural Analysis of Chemokine Receptor-Ligand Interactions". J Med Chem. 60 (12): 4735–4779. PMID 28165741.
External links
- "Chemokine Receptors: CXCR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Human CXCR4 genome location and CXCR4 gene details page in the UCSC Genome Browser.
- Human LAP3 genome location and LAP3 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P61073 (C-X-C chemokine receptor type 4) at the PDBe-KB.