CXC chemokine receptors explained

CXCR1
Symbol:IL8RA
Entrezgene:3577
Omim:146929
Refseq:NM_000634
Uniprot:P25024
Chromosome:2
Arm:q35
CXCR2
Symbol:IL8RB
Entrezgene:3579
Omim:146928
Refseq:NM_001557
Uniprot:P25025
Chromosome:2
Arm:q35
CXCR3
Symbol:CXCR3
Entrezgene:2833
Omim:300574
Refseq:NM_001504
Uniprot:P49682
Chromosome:X
Arm:q13
CXCR4
Symbol:CXCR4
Entrezgene:7852
Omim:162643
Refseq:NM_001008540
Uniprot:P61073
Chromosome:2
Arm:q21
CXCR5
Symbol:BLR1
Entrezgene:643
Omim:601613
Refseq:NM_001716
Uniprot:P32302
Chromosome:11
Arm:q23
CXCR6
Symbol:CXCR6
Entrezgene:10663
Omim:605163
Refseq:NM_006564
Uniprot:O00574
Chromosome:3
Arm:p21

CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.[1] [2]

CXCR1 and CXCR2

CXCR1 and CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as interleukin-8) and CXCL6 can both bind CXCR1 in humans, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2.[3] [4] They are both expressed on the surface of neutrophils in mammals.

CXCR3

CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes [some [[B cell]]s (B lymphocytes) and NK cells] and is highly induced following cell activation. There are two isoforms, CXCR3-A and CXCR3-B.[5] It has three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11.[6] [7]

CXCR4

CXCR4 (also known as fusin) is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 to gain entry into target cells. This receptor has a wide cellular distribution, with expression on most immature and mature hematopoietic cell types (e.g. neutrophils, monocytes, T and B cells, dendritic cells, Langerhans cells and macrophages). In addition, CXCR4 can also be found on vascular endothelial cells and neuronal/nerve cells.

CXCR5

The chemokine receptor CXCR5 is expressed on B cells and CD4+ Tfh cells and is involved in lymphocyte homing and the development of normal lymphoid tissue. Its principal ligand is CXCL13 (or BLC).[8]

CXCR6

CXCR6 was formerly called three different names (STRL33, BONZO, and TYMSTR) before being assigned CXCR6 based on its chromosomal location (within the chemokine receptor cluster on human chromosome 3p21) and its similarity to other chemokine receptors in its gene sequence. CXCR6 binds the ligand CXCL16. However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors.

History

ACKR3 was originally called RDC-1 (an orphan receptor) but has since been shown to cause chemotaxis in T lymphocytes in response to CXCL12 (the ligand for CXCR4) prompting the renaming of this molecule as CXCR7.[9] ACKR3 designation has been accepted by the IUIS/WHO Subcommittee on Chemokine Nomenclature.[1] This receptor has also been identified on memory B cells.

External links

Notes and References

  1. Bachelerie. Françoise. Graham. Gerard J. Locati. Massimo. Mantovani. Alberto. Murphy. Philip M. Nibbs. Robert. Rot. Antal. Sozzani. Silvano. Thelen. Marcus. An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15. British Journal of Pharmacology. 172. 16. 2015. 3945–3949. 0007-1188. 10.1111/bph.13182 . 25958743 . 4543604. free.
  2. Web site: Gene group: C-X-C motif chemokine receptors (CXCR). .
  3. Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH . The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration . Cell . 110 . 3 . 373–83 . August 2002 . 12176324 . 10.1016/s0092-8674(02)00838-3. 16880392 . free .
  4. Pelus LM, Fukuda S . Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties . Experimental Hematology . 34 . 8 . 1010–20 . August 2006 . 16863907 . 10.1016/j.exphem.2006.04.004 . free .
  5. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P . An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4 . The Journal of Experimental Medicine . 197 . 11 . 1537–49 . June 2003 . 12782716 . 2193908 . 10.1084/jem.20021897 .
  6. Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R . Human IP-9: A keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3) . The Journal of Investigative Dermatology . 112 . 5 . 716–22 . May 1999 . 10233762 . 10.1046/j.1523-1747.1999.00581.x . free .
  7. Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD . The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions . Biochemistry . 41 . 33 . 10418–25 . August 2002 . 12173928 . 10.1021/bi026020q.
  8. Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B . B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5 . The Journal of Experimental Medicine . 187 . 4 . 655–60 . February 1998 . 9463416 . 2212150 . 10.1084/jem.187.4.655.
  9. Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F . The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes . The Journal of Biological Chemistry . 280 . 42 . 35760–6 . October 2005 . 16107333 . 10.1074/jbc.M508234200 . free .