Epstein-Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions
Epstein-Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions
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DOI：
10.1038/sj.onc.1202144
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发表时间：
1998-11-05
期刊：
影响因子：
8
通讯作者：
Rowe, M
中科院分区：
文献类型：
--
作者：
Floettmann, JL;Eliopoulos, AG;Rowe, M
EB病毒（EBV）编码的潜伏膜蛋白-1（LMP 1）模拟组成型活性受体分子，并且已经显示激活NF-κ B以及MAPK和JNK途径。已经发现LMP 1的胞质结构域内的两个区域影响细胞信号传导。其中一个羧基末端活化区1（CTAR 1）结合TRAF蛋白家族的成员，另一个（CTAR 2）结合TRADD，表明LMP 1与肿瘤坏死因子受体家族的受体类似地转导信号，能够结合TRAF，激活NF-κ B和JNK途径，上调细胞基因如CD 54 LMP 1信号传导与CD 40信号传导相似，甚至相同。然而，我们现在表明，虽然配体诱导的CD 40信号传导在Jurkat T细胞系中受损，但LMP 1是完全功能性的;因此证明LMP 1和CD 40信号传导不同，其中CTAR 1和CTAR 2结构域中的一个或另一个是非功能性的突变的LMP 1基因在不能上调Jurkat细胞中的CD 54细胞表面标志物方面表现得更像CD 40。然而，LMP 1的CTAR 1结构域，其与CD 40共享TRAF结合序列基序，与CD 40的不同之处在于不能激活Jurkat中的NF-κ B。LMP 1突变体的共转染实验证明CTAR 1可以与CTAR 2在单独的LMP 1分子上合作，只要它们存在于相同的寡聚复合物中。
The Epstein-Barr virus (EBV) encoded Latent Membrane Protein-1 (LMP1) mimics a constitutively active receptor molecule, and has been shown to activate NF-kappa B and the MAPK and JNK pathways, Two regions within the cytosolic domain of LMP1 have been found to effect cell signalling. One of these, the carboxy-terminal activation region-1 (CTAR1), binds members of the TRAF family of proteins, and the other (CTAR2) binds TRADD, suggesting that LMP1 transduces signals similarly to the Tumour Necrosis Factor Receptor family of receptors, The ability to bind TRAFs, to activate NF-kappa B and the JNK pathway, to upregulate cellular genes such as CD54 (ICAM-1 adhesion molecule), and to affect cell growth and apoptosis has led to the suggestion that LMP1 signalling is similar to, or even identical to CD40, However, we now show that while ligand-induced CD40 signalling is impaired in the Jurkat T cell line, LMP1 was fully functional; therefore demonstrating that LMP1 and CD40 signalling differ, Mutated LMP1 genes, in which one or other of the CTAR1 and CTAR2 domains was non-functional, behaved more like CD40 in being unable to upregulate the CD54 cell surface marker in Jurkat cells, However, the CTAR1 domain of LMP1, which shared a TRAF-binding sequence motif with CD40, differed from CD40 in being unable to activate NF-kappa B in Jurkat, Cotransfection experiments with LMP1 mutants demonstrated that CTAR1 can cooperative with CTAR2 on separate LMP1 molecules, provided that they exist within the same oligomeric complex.