CXC chemokine receptors

CXC chemokine receptorsare 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 seven known CXC chemokine receptors in mammals, named CXCR1 through CXCR7.

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.[1][2]They are both expressed on the surface of neutrophils in mammals.

CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes [some B cells (B lymphocytes) and NK cells] and is highly induced following cell activation.There are two isoforms, CXCR3-A and CXCR3-B.[3]It has three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11.[4][5]

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.

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).[6]

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.

CXCR7 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.[7]CXCR7 was recently renamed ACKR3. There is no information publicly available to confirm whether this designation has been accepted by the IUIS/WHO Subcommittee on Chemokine Nomenclature at this time. This receptor has also been identified on memory B cells.

Text under investigation

  1. ^Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH (August 2002). “The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration”. Cell. 110(3): 373–83.  12176324.
  2. ^Pelus LM, Fukuda S (August 2006). “Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties”. Experimental Hematology. 34(8): 1010–20. doi:10.1016/j.exphem.2006.04.004.  16863907.
  3. ^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 (June 2003). “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. doi:10.1084/jem.20021897.  2193908. 12782716.
  4. ^Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R (May 1999). “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. doi:10.1046/j.1523-1747.1999.00581.x.  10233762.
  5. ^Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD (August 2002). “The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions”. Biochemistry. 41(33): 10418–25.  12173928.
  6. ^Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B (February 1998). “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. PMC 2212150.  9463416.
  7. ^Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (October 2005). “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. doi:10.1074/jbc.M508234200.  16107333.
  • “Chemokine Receptors”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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