CXCR7

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CXCR7
Properties of human protein
Mass / length primary structure 362 AS ; 39.7  kDa
Secondary to quaternary structure 7TM
Identifier
Gene names CXCR7 , RDC 1, GPR 159, CMKOR 1
External IDs
Occurrence
Parent taxon Vertebrates

CXCR7 (short for CXC motif chemokine receptor 7 ) is a receptor protein from the chemokine receptor family that occurs on the cell membrane of various cells of the blood-forming system, such as monocytes , basophils, and B lymphocytes . Although it can be phylogenetically and structurally assigned to the G protein-coupled receptor due to its seven helices spanning the cell membrane , it is not directly capable of transmitting signals via G proteins . Activation of the receptor by the chemokines CXCL11 and CXCL12 has been associated with the growth and metastasis of various tumors .

Occurrence

Within the hematopoietic system, CXCR7 can be detected in particular on monocytes, basophilic granulocytes and B-lymphocytes. Different expression rates can be detected on different populations of dendritic cells and T lymphocytes . Laboratory cell lines such as CHO cells and HEK293 cells also express CXCR7.

biochemistry

structure

CXCR7 is a transmembrane protein from the group of G-protein-coupled receptors that is encoded by a gene on chromosome 2 gene locus q37. The gene is located in a cluster of chromosome 2, which also contains the genes of other chemokine receptors, such as CXCR1 , CXCR2 and CXCR4 . In its amino acid sequence , CXCR7 is related to these receptors and shows a sequence agreement of over 40% with CXCR2. A heptahelical structure characteristic of G protein-coupled receptors is assumed.

Receptor activation and signal transduction

CXCR7 is a G protein-coupled receptor to which the chemokines CXCL11 and CXCL12 selectively bind as endogenous ligands. As a consequence of the ligand binding, no direct activation of G proteins can be observed. Therefore, similar to the chemokine receptors DARC and D6 , CXCR7 is considered to be a chemokine scavenger. Regardless of this, a CXCR7-mediated induction of cell adhesion and chemotaxis could be observed in some model systems . These effects are with an activation of alternative signaling pathways involving β-arrestin and the protein kinase B associated. In addition, a modulation of signal transduction pathways through interaction with the chemokine receptor CXCR4 could be shown.

function

The physiological role of CXCR7 in the organism is controversial. Due to the lack of activation of classic signal transduction pathways of G-protein-coupled receptors, a function as a chemokine catcher or chemokine store is suspected. Regardless, CXCR7 is involved in organogenesis .

The expression of CXCR7 on tumor cells suggests a possible role of the receptor in tumorigenesis. In animal experiments, a promotion of tumor growth and metastasis could be demonstrated. Like other chemokine receptors, such as CCR5 and CXCR4 in particular , CXCR7 can serve as a co-receptor for cell penetration in addition to CD4 for some HIV strains .

Individual evidence

  1. ↑ Heesen M, Berman MA, Charest A, Housman D, Gerard C, Dorf ME: Cloning and chromosomal mapping of an orphan chemokine receptor: mouse RDC1 . In: Immunogenetics . 47, No. 5, April 1998, pp. 364-370. PMID 9510554 .
  2. ↑ Balabanian K, Lagane B, Infantino S, et al. : The chemokine SDF-1 / CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes . In: J. Biol. Chem. . 280, No. 42, October 2005, pp. 35760-35766. doi : 10.1074 / jbc.M508234200 . PMID 16107333 .
  3. ↑ a b Thelen M, Thelen S: CXCR7, CXCR4 and CXCL12: an eccentric trio? . In: J. Neuroimmunol. . 198, No. 1-2, July 2008, pp. 9-13. doi : 10.1016 / j.jneuro in 2008.04.020 . PMID 18533280 .
  4. ↑ a b Miao Z, Luker KE, Summers BC, et al. : CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature . In: Proc. Natl. Acad. Sci. USA . 104, No. 40, October 2007, pp. 15735-15740. doi : 10.1073 / pnas.0610444104 . PMID 17898181 . PMC 1994579 (free full text).
  5. ↑ Luker KE, Gupta M, Steele JM, Foerster BR, Luker GD: Imaging ligand-dependent activation of CXCR7 . In: Neoplasia . 11, No. 10, October 2009, pp. 1022-1035. PMID 19794961 . PMC 2745668 (free full text).
  6. ↑ a b Sierro F, Biben C, Martínez-Muñoz L, et al. : Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12 / SDF-1 receptor, CXCR7 . In: Proc. Natl. Acad. Sci. USA . 104, No. 37, September 2007, pp. 14759-14764. doi : 10.1073 / pnas.0702229104 . PMID 17804806 . PMC 1976222 (free full text).
  7. ↑ Wang J, Shiozawa Y, Wang J, et al. : The role of CXCR7 / RDC1 as a chemokine receptor for CXCL12 / SDF-1 in prostate cancer . In: J. Biol. Chem. . 283, No. 7, February 2008, pp. 4283-4294. doi : 10.1074 / jbc.M707465200 . PMID 18057003 .
  8. ↑ Shimizu N, Soda Y, Kanbe K, et al. : A putative G protein-coupled receptor, RDC1, is a novel coreceptor for human and simian immunodeficiency viruses . In: J. Virol. . 74, No. 2, January 2000, pp. 619-626. PMID 10623723 . PMC 111581 (free full text).