The Drosophila atypical protein kinase C-Ref(2)P complex constitutes a conserved module for signaling in the toll pathway
The Drosophila atypical protein kinase C-Ref(2)P complex constitutes a conserved module for signaling in the toll pathway
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DOI：
10.1128/mcb.22.24.8787-8795.2002
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发表时间：
2002-12-01
影响因子：
5.3
通讯作者：
Moscat, J
中科院分区：
文献类型：
--
作者：
Avila, A;Silverman, N;Moscat, J
最近的研究结果表明，哺乳动物p62-非典型蛋白激酶C（aPKC）复合物在NF-κ B活化中的关键作用，以响应不同的刺激。在这里，我们证明了使用RNA干扰技术对施耐德细胞的果蝇aPKC（DaPKC）的Toll信号通路，激活NF-κ B同系物Dif和Dorsal的刺激是必需的。然而，DaPKC似乎并不重要的其他果蝇NF-κ B信号级联，激活NF-κ B同系物Relish响应脂多糖。有趣的是，DaPKC在Dorsal或Dif的核转位下游起作用，控制Drosomycin启动子的转录活性。我们还表明，果蝇Ref（2）P蛋白是哺乳动物p62的同源物，因为它与DaPKC结合，它的过表达足以激活Drosomycin启动子，但不能激活Attacin启动子，它的缺失严重损害Toll信号传导。总之，这些结果表明，保护p62-aPKC复合物的控制先天免疫信号转导的果蝇。
Recent results showed the critical role of the mammalian p62-atypical protein kinase C (aPKC) complex in the activation of NF-kappaB in response to different stimuli. Here we demonstrate using the RNA interference technique on Schneider cells that the Drosophila aPKC (DaPKC) is required for the stimulation of the Toll-signaling pathway, which activates the NF-kappaB homologues Dif and Dorsal. However, DaPKC does not appear to be important for the other Drosophila NF-kappaB signaling cascade, which activates the NF-kappaB homologue Relish in response to lipopolysaccharides. Interestingly, DaPKC functions downstream of the nuclear translocation of Dorsal or Dif, controlling the transcriptional activity of the Drosomycin promoter. We also show that the Drosophila Ref(2)P protein is the homologue of mammalian p62 as it binds to DaPKC, its overexpression is sufficient to activate the Drosomycin but not the Attacin promoter, and its depletion severely impairs Toll signaling. Collectively, these results demonstrate the conservation of the p62-aPKC complex for the control of innate immunity signal transduction in Drosophila melanogaster.