Regulation of Nod1-mediated signaling pathways
Regulation of Nod1-mediated signaling pathways
复制标题
DOI：
10.1038/sj.cdd.4402070
复制
发表时间：
2007-04-01
影响因子：
12.4
通讯作者：
Ulevitch, R. J.
中科院分区：
文献类型：
--
作者：
Correia, J. da Silva;Miranda, Y.;Ulevitch, R. J.
Nod 1是NLR/Nod/CATERPILLER家族的成员。它通过识别来自肽聚糖的特异性糖肽，作为细胞内细菌的传感器。Nod 1激活介导不同的细胞反应，包括激活MAP激酶，IL-8释放，细胞凋亡和抑制MCF-7细胞中的几种雌激素依赖性反应。在这里，我们通过确定Nod 1依赖性信号通路中的关键调控步骤来扩展这些研究。我们提供了多条数据线，表明Nod 1依赖性细胞凋亡是caspase 8介导的事件，细胞凋亡需要RIP 2。相反，一些证据表明Nod 1依赖性JNK激活和IL-8产生不需要caspase 8的存在，但需要TAK 1和RIP 2的激活。因此，我们已经确定了几个关键的控制点，位于下游的节点1。本研究为进一步研究Nod 1信号通路的生物学意义和调控奠定了基础。
Nod1 is a member of the NLR/Nod/CATERPILLER family. It acts as a sensor for intracellular bacteria by recognizing specific glycopeptides derived from peptidoglycan. Nod1 activation mediates distinct cellular responses including activation of MAP kinases, IL-8 release, apoptosis and suppression of several estrogen-dependent responses in MCF-7 cells. Here we have extended these studies by identifying key regulatory steps in Nod1-dependent signaling pathways. We provide multiple lines of data showing that Nod1-dependent apoptosis is a caspase 8-mediated event and that apoptosis requires RIP2. In contrast, several lines of evidence show that Nod1-dependent JNK activation and IL-8 production did not require the presence of caspase 8 but required activation of TAK1 as well as RIP2. Thus, we have identified several key control points that lie downstream of Nod1. This work provides the basis for further studies of the biological significance and regulation of the Nod1 pathway.