Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway C A
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Mol Cell. 1998 Aug;2(2):253-8. doi: 10.1016/s1097-2765(00)80136-7.
The Toll-mediated signaling cascade using the NF-kappaB pathway has been shown to be essential for immune responses in adult Drosophila, and we recently reported that a human homolog of the Drosophila Toll protein induces various immune response genes via this pathway. We now demonstrate that signaling by the human Toll receptor employs an adaptor protein, MyD88, and induces activation of NF-kappaB via the Pelle-like kinase IRAK and the TRAF6 protein, similar to IL-1R-mediated NF-kappaB activation. However, we find that Toll and IL-1R signaling pathways are not identical with respect to AP-1 activation. Finally, our findings implicate MyD88 as a general adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity.
使用NF-κB途径的Toll介导的信号级联反应已被证明对成年果蝇的免疫反应至关重要,并且我们最近报道果蝇Toll蛋白的一种人类同源物通过该途径诱导各种免疫反应基因。我们现在证明,人类Toll受体的信号传导利用衔接蛋白MyD88,并通过类Pelle激酶IRAK和TRAF6蛋白诱导NF-κB的激活,这类似于IL-1R介导的NF-κB激活。然而,我们发现Toll和IL-1R信号通路在AP-1激活方面并不相同。最后,我们的研究结果表明MyD88是先天性免疫的Toll/IL-1R受体家族的一种通用衔接/调节分子。