CXCR3

CXCR3
識別號
別名	CXCR3；, CD183, CKR-L2, CMKAR3, GPR9, IP10-R, Mig-R, MigR, C-X-C motif chemokine receptor 3, CD182
外部ID	OMIM：300574 MGI：1277207 HomoloGene：1153 GeneCards：CXCR3
基因位置（人類）
染色體	X染色體
終止	71,618,511 bp
基因位置（小鼠）
染色體	小鼠X染色體
終止	100,777,875 bp
RNA表現模式
	; ;
	查閱更多表現資料
基因本體
分子功能	• C-X-C chemokine receptor activity; • G protein-coupled receptor activity; • C-X-C chemokine binding; • signal transducer activity; • chemokine binding; • chemokine receptor activity; • 血漿蛋白結合; • signaling receptor activity; • C-C chemokine receptor activity; • C-C chemokine binding;
細胞組分	• 細胞質; • integral component of membrane; • 膜; • integral component of plasma membrane; • cell surface; • external side of plasma membrane; • 細胞膜; • 胞內;
生物學過程	• negative regulation of execution phase of apoptosis; • positive regulation of execution phase of apoptosis; • positive regulation of cytosolic calcium ion concentration; • T cell chemotaxis; • chemokine-mediated signaling pathway; • positive regulation of release of sequestered calcium ion into cytosol; • positive regulation of cAMP-mediated signaling; • regulation of leukocyte migration; • positive regulation of angiogenesis; • negative regulation of endothelial cell proliferation; • cell surface receptor signaling pathway; • 細胞粘附; • positive regulation of chemotaxis; • 血管新生; • positive regulation of cell population proliferation; • chemokine (C-C motif) ligand 11 production; • negative regulation of angiogenesis; • inflammatory response; • calcium-mediated signaling; • positive regulation of transcription by RNA polymerase II; • 訊息傳遞; • 細胞凋亡; • 趨化性; • G protein-coupled receptor signaling pathway; • adenylate cyclase-activating G protein-coupled receptor signaling pathway; • 免疫反應; • cell chemotaxis; • regulation of cell adhesion;
	Sources:Amigo / QuickGO
直系同源
	2833
	12766
	ENSG00000186810
	ENSMUSG00000050232
	P49682
	O88410
	NM_001142797; NM_001504
	NM_009910
	NP_001136269; NP_001495
	NP_034040
	維基資料
檢視/編輯人類	檢視/編輯小鼠

趨化因子受體CXCR3是G蛋白偶連的七跨膜域受體，可選擇性地與CXC趨化因子（CXCL9，CXCL10，和CXCL11）結合^[5]。 CXCR3又稱G蛋白偶聯受體9(GPR9)和CD183。有兩種變異的CXCR3受體。CXCR3－A與CXCL9， CXCL10，CXCL11結合；而CXCR3-B除了與CXCL9， CXCL10，CXCL11結合外還可以與CXCL4結合^[6]。

表現

CXCR3主要表現在T細胞、自然殺手細胞活性上^[7]，有的上皮細胞和一些內皮細胞也表現CXCR3。 I型輔助T細胞（Th1）優先表現CXCR3及CCR5^[7]，而II型輔助T細胞（Th2）表現CCR3和CCR4。 CXCR3與配位基結合後在誘導I型輔助T細胞（Th1）遷移的同時又阻止II型輔助T細胞（Th2）的遷徙。從而增強T細胞的分化效應。

信號傳遞

CXCR3與其配位基CXCL9， CXCL10，CXCL11的結合，能引起細胞鈣離子的內流，啟動肌醇磷脂3-激酶和絲裂原活化蛋白激酶（MAPK）^[8]。詳細的信號通路尚未確立，但與其他的趨化因子受體的信號傳遞有類似的激酶。

功能

CXCR3調節白血球遷徙。CXCR3與配位基相互作用引起I型輔助T細胞（Th1）的遷移，並促進I型輔助T細胞（Th1）成熟。

疾病

CXCR3可能在下列疾病中起作用，包括動脈粥樣硬化^[9]、多發性硬化^[10]、肺纖維化^[11]、I型糖尿病^[12]、重症肌無力、急性心臟移植排斥^[13]。開發阻斷CXCR3與其配位基相互作用的藥物可提供治療這些疾病的新途徑。

參見

參考文獻

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000186810 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000050232 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Clark-Lewis, Ian; Mattioli, Ivan; Gong, Jiang-Hong; Loetscher, Pius. Structure-function relationship between the human chemokine receptor CXCR3 and its ligands. The Journal of Biological Chemistry. 2003-01-03, 278 (1): 289–295. ISSN 0021-9258. PMID 12417585. doi:10.1074/jbc.M209470200 .
^ Lasagni, Laura; Francalanci, Michela; Annunziato, Francesco; Lazzeri, Elena; Giannini, Stefano; Cosmi, Lorenzo; Sagrinati, Costanza; Mazzinghi, Benedetta; Orlando, Claudio; Maggi, Enrico; Marra, Fabio; Romagnani, Sergio; Serio, Mario; Romagnani, Paola. 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. 2003-06-02, 197 (11): 1537–1549. ISSN 0022-1007. PMC 2193908 . PMID 12782716. doi:10.1084/jem.20021897 .
^ ^7.0 ^7.1 Qin, S.; Rottman, J. B.; Myers, P.; Kassam, N.; Weinblatt, M.; Loetscher, M.; Koch, A. E.; Moser, B.; Mackay, C. R. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. The Journal of Clinical Investigation. 1998-02-15, 101 (4): 746–754. ISSN 0021-9738. PMC 508621 . PMID 9466968. doi:10.1172/JCI1422 .
^ Smit, Martine J.; Verdijk, Pauline; van der Raaij-Helmer, Elisabeth M. H.; Navis, Marjon; Hensbergen, Paul J.; Leurs, Rob; Tensen, Cornelis P. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood. 2003-09-15, 102 (6): 1959–1965. ISSN 0006-4971. PMID 12750173. doi:10.1182/blood-2002-12-3945.
^ Mach, F.; Sauty, A.; Iarossi, A. S.; Sukhova, G. K.; Neote, K.; Libby, P.; Luster, A. D. Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. The Journal of Clinical Investigation. 1999, 104 (8): 1041–1050. ISSN 0021-9738. PMC 408576 . PMID 10525042. doi:10.1172/JCI6993 .
^ Sørensen, T. L.; Tani, M.; Jensen, J.; Pierce, V.; Lucchinetti, C.; Folcik, V. A.; Qin, S.; Rottman, J.; Sellebjerg, F.; Strieter, R. M.; Frederiksen, J. L.; Ransohoff, R. M. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. The Journal of Clinical Investigation. 1999, 103 (6): 807–815. ISSN 0021-9738. PMC 408141 . PMID 10079101. doi:10.1172/JCI5150 .
^ Jiang, Dianhua; Liang, Jiurong; Hodge, Jennifer; Lu, Bao; Zhu, Zhou; Yu, Shuang; Fan, Juan; Gao, Yunfei; Yin, Zhinan; Homer, Robert; Gerard, Craig; Noble, Paul W. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. The Journal of Clinical Investigation. 2004, 114 (2): 291–299. ISSN 0021-9738. PMC 449741 . PMID 15254596. doi:10.1172/JCI16861 .
^ Frigerio, Simona; Junt, Tobias; Lu, Bao; Gerard, Craig; Zumsteg, Urs; Holländer, Georg A.; Piali, Luca. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nature Medicine. 2002, 8 (12): 1414–1420. ISSN 1078-8956. PMID 12415259. doi:10.1038/nm1202-792.
^ Hancock, W. W.; Lu, B.; Gao, W.; Csizmadia, V.; Faia, K.; King, J. A.; Smiley, S. T.; Ling, M.; Gerard, N. P.; Gerard, C. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. The Journal of Experimental Medicine. 2000-11-20, 192 (10): 1515–1520. ISSN 0022-1007. PMC 2193193 . PMID 11085753. doi:10.1084/jem.192.10.1515 .

外部連結

Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006 Feb 9;354(6):610-21.（頁面存檔備份，存於網際網路檔案館）

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000186810 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000050232 - 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.

[leo-5] Clark-Lewis, Ian; Mattioli, Ivan; Gong, Jiang-Hong; Loetscher, Pius. Structure-function relationship between the human chemokine receptor CXCR3 and its ligands. The Journal of Biological Chemistry. 2003-01-03, 278 (1): 289–295. ISSN 0021-9258. PMID 12417585. doi:10.1074/jbc.M209470200 .

[6] Lasagni, Laura; Francalanci, Michela; Annunziato, Francesco; Lazzeri, Elena; Giannini, Stefano; Cosmi, Lorenzo; Sagrinati, Costanza; Mazzinghi, Benedetta; Orlando, Claudio; Maggi, Enrico; Marra, Fabio; Romagnani, Sergio; Serio, Mario; Romagnani, Paola. 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. 2003-06-02, 197 (11): 1537–1549. ISSN 0022-1007. PMC 2193908 . PMID 12782716. doi:10.1084/jem.20021897 .

[qin-7] 7.0 ^7.1 Qin, S.; Rottman, J. B.; Myers, P.; Kassam, N.; Weinblatt, M.; Loetscher, M.; Koch, A. E.; Moser, B.; Mackay, C. R. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. The Journal of Clinical Investigation. 1998-02-15, 101 (4): 746–754. ISSN 0021-9738. PMC 508621 . PMID 9466968. doi:10.1172/JCI1422 .

[8] Smit, Martine J.; Verdijk, Pauline; van der Raaij-Helmer, Elisabeth M. H.; Navis, Marjon; Hensbergen, Paul J.; Leurs, Rob; Tensen, Cornelis P. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood. 2003-09-15, 102 (6): 1959–1965. ISSN 0006-4971. PMID 12750173. doi:10.1182/blood-2002-12-3945.

[9] Mach, F.; Sauty, A.; Iarossi, A. S.; Sukhova, G. K.; Neote, K.; Libby, P.; Luster, A. D. Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. The Journal of Clinical Investigation. 1999, 104 (8): 1041–1050. ISSN 0021-9738. PMC 408576 . PMID 10525042. doi:10.1172/JCI6993 .

[10] Sørensen, T. L.; Tani, M.; Jensen, J.; Pierce, V.; Lucchinetti, C.; Folcik, V. A.; Qin, S.; Rottman, J.; Sellebjerg, F.; Strieter, R. M.; Frederiksen, J. L.; Ransohoff, R. M. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. The Journal of Clinical Investigation. 1999, 103 (6): 807–815. ISSN 0021-9738. PMC 408141 . PMID 10079101. doi:10.1172/JCI5150 .

[11] Jiang, Dianhua; Liang, Jiurong; Hodge, Jennifer; Lu, Bao; Zhu, Zhou; Yu, Shuang; Fan, Juan; Gao, Yunfei; Yin, Zhinan; Homer, Robert; Gerard, Craig; Noble, Paul W. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. The Journal of Clinical Investigation. 2004, 114 (2): 291–299. ISSN 0021-9738. PMC 449741 . PMID 15254596. doi:10.1172/JCI16861 .

[12] Frigerio, Simona; Junt, Tobias; Lu, Bao; Gerard, Craig; Zumsteg, Urs; Holländer, Georg A.; Piali, Luca. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nature Medicine. 2002, 8 (12): 1414–1420. ISSN 1078-8956. PMID 12415259. doi:10.1038/nm1202-792.

[13] Hancock, W. W.; Lu, B.; Gao, W.; Csizmadia, V.; Faia, K.; King, J. A.; Smiley, S. T.; Ling, M.; Gerard, N. P.; Gerard, C. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. The Journal of Experimental Medicine. 2000-11-20, 192 (10): 1515–1520. ISSN 0022-1007. PMC 2193193 . PMID 11085753. doi:10.1084/jem.192.10.1515 .

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