Vogel Stefanie N, Fitzgerald Katherine A, Fenton Matthew J
Departments of Microbiology and Immunology and Medicine, University of Maryland, Baltimore, MD, USA.
Mol Interv. 2003 Dec;3(8):466-77. doi: 10.1124/mi.3.8.466.
In response to microbial or environmental "danger" signals, represented by structural motifs not normally expressed by cells, Toll-like receptors mediate intracellular signaling that leads to inflammatory gene expression. In response to agonists, TLR aggregation enables the recruitment and/or activation of TLR-specific adapter molecules. To date, four adapter proteins have been identified: MyD88, TIRAP/Mal, TRIF/TICAM-1, and TIRP/TRAM/TICAM-2. The interaction of the different TLRs with distinct combinations of adapter molecules creates a platform to which additional kinases, transacting factors, and possibly other molecules are recruited, events that lead, ultimately, to gene expression. Given the rapidity with which such interactions have been described, we have attempted to summarize our current understanding of the adapters that are so essential for TLR signaling and provide a working model for future studies.
细胞通常不会表达的结构基序所代表的微生物或环境“危险”信号，可激活Toll样受体，介导细胞内信号传导，进而导致炎症基因表达。在激动剂的作用下，Toll样受体聚集能够募集和/或激活Toll样受体特异性衔接分子。迄今为止，已鉴定出四种衔接蛋白：髓样分化因子88（MyD88）、TIR结构域衔接蛋白/髓样分化因子88接头样蛋白（TIRAP/Mal）、Toll样受体相关接头蛋白诱导干扰素β/含TIR结构域衔接分子1（TRIF/TICAM-1）以及含TIR结构域的接头蛋白/TRIF相关分子/TICAM-2（TIRP/TRAM/TICAM-2）。不同的Toll样受体与不同组合的衔接分子相互作用，形成了一个平台，其他激酶、反式作用因子以及可能的其他分子被募集到该平台上，这些事件最终导致基因表达。鉴于此类相互作用的描述速度之快，我们试图总结目前对Toll样受体信号传导所必需的衔接蛋白的理解，并为未来研究提供一个工作模型。
