Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins
Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins
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DOI：
10.1093/emboj/18.11.3064
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发表时间：
1999-06-01
期刊：
影响因子：
11.4
通讯作者：
Hammerschmidt, W
中科院分区：
文献类型：
--
作者：
Gires, O;Kohlhuber, F;Hammerschmidt, W
潜伏膜蛋白1(LMP1)类似于肿瘤坏死因子受体超家族的一个永久激活的受体，是EB病毒使B细胞永生所必需的。分子和生物化学方法表明，LMP1通过两个C端活化区侵占细胞信号通路，导致核因子-kappaB和AP-1的诱导。我们在这里证明了在LMP1‘S C-末端33bp的重复延伸中包含一个富含Pro的序列的第三个区域是Janus kinase3(JAK3)激活所必需的。LMP1和JAK3的相互作用导致条件NGF-R：LMP1嵌合体交联后几分钟内JAK3的酪氨酸自动/转磷酸化增强，这是STAT转录因子激活的先决条件。这些结果揭示了LMP1C末端的一个新的活化区，并确认JAK/STAT通路是这种病毒整合膜蛋白在B细胞中的靶标。
Latent membrane protein 1 (LMP1) acts like a permanently activated receptor of the tumor necrosis factor (TNF)-receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus. Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappa B and AP-1 via two C-terminal activating regions. We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1's C-terminus is required for the activation of Janus kinase 3 (JAK3). The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R:LMP1 chimera and is a prerequisite for the activation of STAT transcription factors. These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK/STAT pathway as a target of this viral integral membrane protein in B cells.