Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants
Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants
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DOI：
10.1002/jlb.63.6.650
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发表时间：
1998-06-01
影响因子：
5.5
通讯作者：
Greene, C
中科院分区：
文献类型：
--
作者：
O'Neill, LAJ;Greene, C
白细胞介素-1（IL-1）是免疫和炎症反应的重要调节因子，近年来，IL-1受体及其信号转导的研究取得了重大进展，已发现一个与I型IL-1受体（IL-1 RI）信号转导结构域具有高度同源性的蛋白家族，包括IL-1受体辅助蛋白（IL-1AcP），其不结合IL-1但对IL-1信号传导是必需的;果蝇蛋白Toll;许多人Toll样受体（hTLR）;推定的IL-18/IL-1-γ受体IL-1 Rrp（IL-1受体相关蛋白）;和许多植物蛋白。所有这些似乎都参与了宿主对损伤和感染的反应。这些同源性也延伸到涉及IL-1作用的新型信号蛋白。在果蝇（Pelle）和植物（Pto）中具有同源物的两种IL-1受体相关激酶IRAK-1和IRAK-2涉及转录因子核因子κ B（NF-κ B）的激活。IRAK-1还参与AP 1诱导、Jun氨基末端激酶（JNK）活化和IL-2诱导。它通过与IL-1AcP的相互作用将衔接蛋白TRAF 6募集到IL-1受体复合物。然后TRAF 6通过NF-κ B诱导激酶（NIK）将信号传递给两种I-κ B激酶（IKK-1和-2），导致NF-κ B活化。在其他IL-1应答激酶方面也取得了进展，包括JNK和p38 MAP激酶，后者在对IL-1的多重应答中起作用。不同物种之间的显著保守性表明IL-1系统代表了对环境应激和病原体附着的应答至关重要的古老信号机器。
Interleukin-1 (IL-1) is a central regulator of the immune and inflammatory responses, Recently significant advances have been made in the area of IL-1 receptors and IL-1 signal transduction, A family of proteins has been described that share significant homology in their signaling domains with the Type I IL-1 receptor (IL-1RI), These include the IL-1 receptor accessory protein (IL-1AcP), which does not bind IL-1 but is essential for IL-1 signaling; a Drosophila protein Toll; a number of human Toll-like receptors (hTLRs); the putative IL-18/IL-1-gamma receptor IL-1Rrp (IL-1 receptor-related protein); and a number of plant proteins. All appear to be involved in host responses to injury and infection. These homologies also extend to novel signaling proteins implicated in IL-1 action. Two IL-1 receptor-associated kinases, IRAK-1 and IRAK-2, which have homologs in Drosophila (Pelle) and plants (Pto), have been implicated in the activation of the transcription factor, nuclear factor kappa B (NF-kappa B). IRAK-1 has also been implicated in AP 1 induction, Jun amino-terminal kinase (JNK) activation, and IL-2 induction, It recruits the adapter protein TRAF6 to the IL-1 receptor complex via an interaction with IL-1AcP. TRAF6 then relays the signal via NF-kappa B-inducing kinase (NIK) to two I-kappa B kinases (IKK-1 and -2), leading to NF-KB activation. Progress has also been made on other IL-1-responsive kinases, including JNK and p38 MAP kinase, with the latter having a role in multiple responses to IL-1, The remarkable conservation between diverse species indicates that the IL-1 system represents an ancient signaling machine critical for responses to environmental stresses and attach by pathogens.