通过TRAF3和TRAF6的不同的效应器功能进行通道式受体信号的特异性
Hans Häcker1, Vanessa Redecke, Blagoy Blagoev
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. Hans.Haecker@stjude.org
收费类受体 (TLR) 信号传输涉及像TRAF3和TRAF6.6这样的适配器. TRAF3对于I型干扰素和IL-10的产生至关重要,而TRAF6在先天免疫中具有不同的功能.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 收费类受体 (TLRs) 在检测病原体时启动先天免疫反应.
- 在TLR信号通路中,使用具有Toll/interleukin-1受体 (TIR) 域的适配蛋白.
- 多样化TLR效应器功能的机制仍然不完全理解.
研究的目的:
- 生物化学剖析托尔类受体 (TLR) 信号通路.
- 识别TIR信号综合体的新型组件和功能.
- 阐明TNF受体相关因子3 (TRAF3) 和TRAF6在TLR反应中的不同作用.
主要方法:
- 开发一种系统,以隔离由二元化适配器组装的信号复合体.
- 使用MyD88作为原型适配器对信号复合物的生物化学分析.
- 使用淘汰赛小鼠骨髓细胞对TRAF3和TRAF6的功能性表征.
主要成果:
- 鉴定TNF受体关联因子3 (TRAF3) 是TIR信号复合体的一个新组成部分,与TRAF6.6一起招募.
- 对于I型干扰素 (IFN) 和互白素-10 (IL-10) 诱导,TRAF3是必不可少的,但对于促炎性细胞因子表达是不可或缺的.
- 由于IL-10的产生受损,TRAF3缺乏的细胞表现出过度生产的促炎性细胞因子.
- 需要TRAF3来招募TBK1激酶到含有TRIF的TIR信号复合体中,调解IFN反应.
结论:
- 尽管有结构上的相似之处,TRAF3和TRAF6在很大程度上具有不同的功能.
- 在调节促炎和抗炎细胞因子产生之间的平衡方面,TRAF3起着至关重要的作用.
- 通过其在TBK1招募到TIR复合体中的作用,TRAF3对于I型干扰素诱导是不可或缺的.
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