CXCR4
外觀
趨化因子受體CXCR4是趨化因子基質細胞衍生因子-1(CXCL12)的特異受體[1][2]。CXCL12對淋巴細胞有強烈的趨化作用。該受體是用來提取純化艾滋病毒的幾個趨化因子受體之一。現在還不清楚是否出現使用CXCR4的人類免疫缺乏病毒是免疫缺乏的原因還是後果。
另外,CXCR4還可能人類胚胎發育中的着床過程中起作用。
作為趨化因子受體與配體,CXCR4和CXCL12比較特殊,他們是一配一的受體配體關係。絕大數趨化因子受體有多個配體,一個趨化因子可以結合到兩個或多個受體。
CXCR4的配體CXCL12在造血幹細胞移居骨髓在起重要作用[3]。影響或阻斷CXCR4受體配體結合,可以調節造血幹細胞的遷徙,這對骨髓造血幹細胞移植可能十分有用。目前的試驗藥物有:粒細胞集落刺激因子(Granulocyte colony-stimulating factor)和Plerixafor(AMD3100)。但這些藥物尚未臨床使用。
CXCR4在體內大部分組織和器官上都有表達,它是由352個氨基酸組成的GPCR(G蛋白偶聯受體),具有七次穿膜結構。 CXCR4參與體內多種生理機制,包括參與HIV-1病毒侵染【1】,造血功能【2】,胚胎發育【3-7】,及腫瘤遷移等【8】。
參考文獻
[編輯]- ^ Deng H, et al., Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661-6.
- ^ Oberlin E, et al., The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996 Aug 29;382(6594):833
- ^ Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998 Jun 11;393(6685):595-9.
- Dragic, T., An overview of the determinants of CCR5 and CXCR4 co-receptor function. J Gen Virol, 2001. 82(Pt 8): p. 1807-14.
- Maekawa, T. and T. Ishii, Chemokine/receptor dynamics in the regulation of hematopoiesis. Intern Med, 2000. 39(2): p. 90-100.
- Nagasawa, T., et al., Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 1996. 382(6592): p. 635-8.
- Tachibana, K., et al., The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature, 1998. 393(6685): p. 591-4.
- Zou, Y.R., et al., Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 1998. 393(6685): p. 595-9.
- McGrath, K.E., et al., Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol, 1999. 213(2): p. 442-56.
- Lu, M., E.A. Grove, and R.J. Miller, Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A, 2002. 99(10): p. 7090-5.
- Burger, J.A. and T.J. Kipps, CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood, 2006. 107(5): p. 1761-7.
|