CXCR4

Source: Wikipedia, the free encyclopedia.
CXCR4
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_003467
NM_001008540
NM_001348056
NM_001348059
NM_001348060

NM_009911
NM_001356509

RefSeq (protein)

NP_001008540
NP_003458
NP_001334985
NP_001334988
NP_001334989

NP_034041
NP_001343438

Location (UCSC)Chr 2: 136.11 – 136.12 MbChr 1: 128.52 – 128.52 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a

CXC chemokine receptor.[7]

Function

CXCR-4 is an alpha-

T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.[citation needed
]

CXCR4 is

]

CXCR4's

damage associated molecular pattern molecules.[9] It is speculated this interaction may be through CXCR4 mediated signalling pathways. MIF is an additional ligand of CXCR4[10]

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

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, approved for routine clinical use,[13] which directly blocks the CXCR4 receptor. It is a very efficient inducer of hematopoietic stem cell mobilization in animal and human studies. In a small human clinical trial to evaluate the safety and efficacy of fucoidan ingestion (brown seaweed extract), 3g daily of 75% w/w oral fucoidan for 12 days increased the proportion of CD34+CXCR4+ from 45 to 90% and the serum SDF-1 levels, which could be useful in CD34+ cells homing/mobilization via SDF-1/CXCR4 axis.[14]

It has been associated with

Waldenström's macroglobulinemia, a B-cell malignancy.[16] The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenström's macroglobulinemia.[17]

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.

neutrophils that inhibit seeding of tumor cells in the lung.[21]

Drug response

Chronic exposure to

T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes in rhesus macaques.[22]
It has been shown that BCR signalling inhibitors also affect CXCR4 pathway and thus CD20 expression.

Interactions

CXCR4 has been shown to

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121966 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045382 - 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. S2CID 36552134
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  7. ^ "Gene group: C-X-C motif chemokine receptors (CXCR)". HUGO Gene Nomenclature Committee.
  8. PMID 20228059
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Further reading

External links

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