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ECSIT是Toll/IL-1信号转导通路中一种进化上保守的中间体。

ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway.

作者信息

Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway C A, Ghosh S

机构信息

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.

出版信息

Genes Dev. 1999 Aug 15;13(16):2059-71. doi: 10.1101/gad.13.16.2059.

Abstract

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.

摘要

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。

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