Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway C A, Ghosh S
Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute (HHMI), Yale University School of Medicine, New Haven, Connecticut 06520 USA.
Genes Dev. 1999 Aug 15;13(16):2059-71. doi: 10.1101/gad.13.16.2059.
Activation of NF-kappaB as a consequence of signaling through the Toll and IL-1 receptors is a major element of innate immune responses. We report the identification and characterization of a novel intermediate in these signaling pathways that bridges TRAF6 to MEKK-1. This adapter protein, which we have named ECSIT (evolutionarily conserved signaling intermediate in Toll pathways), is specific for the Toll/IL-1 pathways and is a regulator of MEKK-1 processing. Expression of wild-type ECSIT accelerates processing of MEKK-1, whereas a dominant-negative fragment of ECSIT blocks MEKK-1 processing and activation of NF-kappaB. These results indicate an important role for ECSIT in signaling to NF-kappaB and suggest that processing of MEKK-1 is required for its function in the Toll/IL-1 pathway.
通过Toll和IL-1受体进行信号传导导致的NF-κB激活是先天免疫反应的一个主要因素。我们报告了这些信号通路中一种新型中间体的鉴定和特征，该中间体将TRAF6与MEKK-1连接起来。这种衔接蛋白，我们将其命名为ECSIT（Toll通路中进化保守的信号中间体），对Toll/IL-1通路具有特异性，并且是MEKK-1加工的调节剂。野生型ECSIT的表达加速了MEKK-1的加工，而ECSIT的显性负性片段则阻断了MEKK-1的加工以及NF-κB的激活。这些结果表明ECSIT在向NF-κB的信号传导中起重要作用，并表明MEKK-1的加工是其在Toll/IL-1通路中发挥功能所必需的。
