[PDF][PDF] MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways

R Medzhitov, P Preston-Hurlburt, E Kopp, A Stadlen… - Molecular cell, 1998 - cell.com
R Medzhitov, P Preston-Hurlburt, E Kopp, A Stadlen, C Chen, S Ghosh, CA Janeway
Molecular cell, 1998cell.com
The Toll-mediated signaling cascade using the NF-κB 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-κB via the Pelle-like kinase IRAK and
the TRAF6 protein, similar to IL-1R-mediated NF-κB activation. However, we find that Toll …
Abstract
The Toll-mediated signaling cascade using the NF-κB 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-κB via the Pelle-like kinase IRAK and the TRAF6 protein, similar to IL-1R-mediated NF-κB 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.
cell.com