Dishevelled proteins lead to two signaling pathways - Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells
Dishevelled proteins lead to two signaling pathways - Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells
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DOI：
10.1074/jbc.274.1.129
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发表时间：
1999-01-01
影响因子：
4.8
通讯作者：
Wu, DQ
中科院分区：
文献类型：
--
作者：
Li, L;Yuan, HD;Wu, DQ
已知Dishevelled（Dsh/Dvl）蛋白通过上调β-连环蛋白水平和刺激T细胞因子（TCF）LEF-1依赖性转录来介导Wnt信号传导。我们已经鉴定了一种新的Dvl介导的信号传导途径，即小鼠Dvl蛋白在COS-7细胞中表达时刺激c-Jun依赖性转录活性和c-Jun N-末端激酶（JNK）的激酶活性。相比之下，Dvl的所有三个保守结构域，包括DIX、PDZ和DEP，都是在哺乳动物细胞中上调β-连环蛋白和刺激LEF-1介导的转录所需的。因此，Dvl可以导致两种不同的信号通路。此外，Cdc 42或Rad的小G蛋白，这是参与JNK激活的许多刺激，没有出现Dv 1介导的JNK激活中发挥主要作用，因为显性负突变的Cdc 42和Rad不能抑制Dv 1诱导的JNK激活。这表明Dvl可能通过新的途径激活JNK。
Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK), The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rad, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rad could not inhibit Dv1-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.