CXCR4

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Chemokine (C-X-C motif) receptor 4

CXCR4 in complex with IT1t(PDB 3OE9)
有效結構
PDB 直系同源檢索:PDBe, RCSB
標識
代號 CXCR4; CD184; D2S201E; FB22; HM89; HSY3RR; LAP3; LCR1; LESTR; NPY3R; NPYR; NPYRL; NPYY3R; WHIM
擴展標識 遺傳學162643 鼠基因109563 同源基因20739 IUPHAR:  CXCR4 ChEMBL: 2107 GeneCards: CXCR4 Gene
RNA表達模式
PBB GE CXCR4 217028 at tn.png
PBB GE CXCR4 209201 x at tn.png
PBB GE CXCR4 211919 s at tn.png
更多表達數據
直系同源體
物種 人類 鼠類
Entrez 7852 12767
Ensembl ENSG00000121966 ENSMUSG00000045382
UniProt P61073 P70658
mRNA序列 NM_001008540 NM_009911
蛋白序列 NP_001008540 NP_034041
基因位置 Chr 2:
136.87 – 136.88 Mb
Chr 1:
128.59 – 128.59 Mb
PubMed查詢 [1] [2]

趨化因子受體CXCR4趨化因子基質細胞衍生因子-1CXCL12)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愛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著床過程中起作用。

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)。當然,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個胺基酸組成的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】,胚胎髮育【3-7】,及腫瘤遷移等【8】。

參考文獻[編輯]

  1. ^ Deng H, et al., Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661-6.
  2. ^ 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
  3. ^ 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.
1. Dragic, T., An overview of the determinants of CCR5 and CXCR4 co-receptor function. J Gen Virol, 2001. 82(Pt 8): p. 1807-14.

2. Maekawa, T. and T. Ishii, Chemokine/receptor dynamics in the regulation of hematopoiesis. Intern Med, 2000. 39(2): p. 90-100.

3. 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.

4. Tachibana, K., et al., The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature, 1998. 393(6685): p. 591-4.

5. Zou, Y.R., et al., Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 1998. 393(6685): p. 595-9.

6. 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.

7. 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.

8. 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.