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Structural highlights

Function

CXCR3_HUMAN Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably promotes cell chemotaxis response. Upon activation by PF4, induces activated T-lymphocytes migration mediated via downstream Ras/extracellular signal-regulated kinase (ERK) signaling.^{[1] [2] [3]} Receptor for the C-X-C chemokine CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the proliferation, survival and angiogenic activity of human microvascular endothelial cells (HMVEC) through a cAMP-mediated signaling pathway (PubMed:12782716). Does not promote cell chemotaxis respons. Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK pathway and contributes to inhibition of angiogenesis. Overexpression in renal cancer cells down-regulates expression of the anti-apoptotic protein HMOX1 and promotes apoptosis.^[4] Mediates the activity of CXCL11.

References

1. ↑ 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. J Exp Med. 2003 Jun 2;197(11):1537-49. PMID:12782716 doi:10.1084/jem.20021897
2. ↑ Mueller A, Meiser A, McDonagh EM, Fox JM, Petit SJ, Xanthou G, Williams TJ, Pease JE. CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3. J Leukoc Biol. 2008 Apr;83(4):875-82. PMID:18174362 doi:10.1189/jlb.1006645
3. ↑ Van Raemdonck K, Gouwy M, Lepers SA, Van Damme J, Struyf S. CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular endothelial cells and activated lymphocytes: involvement of mitogen-activated protein (MAP) kinases, Src and p70S6 kinase. Angiogenesis. 2014 Jul;17(3):631-40. PMID:24469069 doi:10.1007/s10456-014-9417-6
4. ↑ 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. J Exp Med. 2003 Jun 2;197(11):1537-49. PMID:12782716 doi:10.1084/jem.20021897