Adaptors in toll-like receptor signaling and their potential as therapeutic targets.
Adaptors in toll-like receptor signaling and their potential as therapeutic targets.
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DOI：
10.2174/138945012803530260
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发表时间：
2012-09
影响因子：
3.2
通讯作者：
T. Ve;N. Gay;A. Mansell;B. Kobe;S. Kellie
中科院分区：
文献类型：
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作者：
T. Ve;N. Gay;A. Mansell;B. Kobe;S. Kellie
为了启动先天免疫应答，Toll样受体（TLR）通过TIR（Toll/白细胞介素-1受体）结构域相互作用与细胞质衔接蛋白缔合。四种主要的信号转导衔接蛋白包括MyD 88、MAL、TRIF和TRAM，第五种蛋白SARM参与TLR途径的负调控，通常被认为是含TIR结构域的衔接蛋白组的一部分。其他含有TIR结构域的蛋白质也显示出调节这些信号传导途径，包括ST 2和SIGIRR，以及作为毒力因子调节这些途径的几种细菌和病毒含有TIR结构域的蛋白质。TLR通路和衔接蛋白与许多疾病相关，包括感染、败血症、炎症、过敏性和自身免疫性疾病以及癌症。本文综述了衔接蛋白及其调控蛋白的结构和功能，它们与疾病的关系及其作为人类疾病治疗靶点的潜力。
To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group. Other TIR domain-containing proteins have also been shown to regulate these signaling pathways, including ST2 and SIGIRR, as well as several bacterial and viral TIR domain-containing proteins that modulate these pathways as virulence factors. TLR pathways and the adaptor proteins are associated with a number of diseases, including infection, sepsis, inflammatory, allergic and autoimmune diseases and cancer. We review our current understanding of the structure and function of adaptor proteins and their regulatory proteins, their association with disease and their potential as therapeutic targets in human disease.