The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense.
The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense.
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DOI：
10.1126/stke.2003.171.re3
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发表时间：
2003-02-25
期刊：
影响因子：
--
通讯作者：
O'Neill, Luke A J
中科院分区：
文献类型：
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作者：
Dunne, Aisling;O'Neill, Luke A J
由于白细胞介素-1（IL-1）在炎症性疾病中的重要作用，其激活的信号转导通路一直是人们关注的焦点。已经描述了许多参与转录因子核因子κ B（NF-κ B）和应激活化蛋白激酶如p38促分裂原活化蛋白激酶（MAPK）的受体后活化的蛋白质。还发现I型IL-1受体（IL-1 RI）是扩展的受体超家族的成员。这些相关受体在其胞质区域都具有序列相似性。该家族包括黑腹果蝇蛋白质Toll、IL-18受体（IL-18 R）和10种Toll样受体（TLR），TLR-1至TLR-10，它们与微生物产物结合，激活宿主防御反应。由于IL-1 RI与Toll的相似性，这些蛋白质胞质区域中的保守序列被称为Toll-IL-1受体（TIR）结构域。在IL-1 RI信号传导过程中激活的相同蛋白质也参与具有TIR结构域的其他受体的信号传导。受体超家族在进化上是保守的;成员也存在于植物和昆虫中，在那里它们也在宿主防御中起作用。被激活的信号蛋白在物种间也是保守的。然而，不同受体激活的信号通路开始出现差异。因此，该受体超家族代表了一个古老的信号系统，是先天免疫和炎症反应的关键决定因素。
The signal transduction pathways activated by the proinflammatory cytokine interleukin-1 (IL-1) have been the focus of much attention because of the important role that IL-1 plays in inflammatory diseases. A number of proteins have been described that participate in the post-receptor activation of the transcription factor nuclear factor kappaB (NF-kappaB), and stress-activated protein kinases such as p38 mitogen-activated protein kinase (MAPK). It has also emerged that the type I IL-1 receptor (IL-1RI) is a member of an expanding receptor superfamily. These related receptors all have sequence similarity in their cytosolic regions. The family includes the Drosophila melanogaster protein Toll, the IL-18 receptor (IL-18R), and 10 Toll-like receptors (TLRs), TLR-1 to TLR-10, which bind to microbial products, activating host defense responses. Because of the similarity of IL-1RI to Toll, the conserved sequence in the cytosolic region of these proteins has been termed the Toll-IL-1 receptor (TIR) domain. The same proteins activated during signaling by IL-1RI also participate in signaling by other receptors with TIR domains. The receptor superfamily is evolutionarily conserved; members also occur in plants and insects, where they also function in host defense. The signaling proteins that are activated are also conserved across species. Differences are, however, starting to emerge in signaling pathways activated by different receptors. This receptor superfamily, therefore, represents an ancient signaling system that is a critical determinant of the innate immune and inflammatory responses.