TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
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DOI：
10.1038/ni1569
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发表时间：
2008-04-01
影响因子：
30.5
通讯作者：
Medzhitov, Ruslan
中科院分区：
文献类型：
--
作者：
Kagan, Jonathan C.;Su, Tian;Medzhitov, Ruslan
Toll样受体4（TLR 4）诱导由TIRAP-MyD 88和TRAM-TRIF对衔接蛋白控制的两种不同的信号传导途径，其分别引起促炎细胞因子和I型干扰素的产生。TLR 4如何协调这两种途径的激活尚不清楚。在这里，我们表明，TLR 4激活这两个信号通路依次在TLR 4复合物的内吞周围组织的过程。我们提出TLR 4首先在质膜上诱导TIRAP-MyD 88信号传导，然后被内吞并激活早期内体的TRAM-TRIF信号传导。我们的数据强调了先天免疫识别的统一主题，即所有I型干扰素诱导受体从细胞内位置发出信号。
Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organized around endocytosis of the TLR4 complex. We propose that TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes. Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location.