MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.
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.
Medzhitov
R
R
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Preston-Hurlburt
P
P
Kopp
E
E
Stadlen
A
A
Chen
C
C
Ghosh
S
S
Janeway
C A
CA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation; D004330:Drosophila; D029721:Drosophila Proteins; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D029721:Drosophila Proteins; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C499312:Myd88 protein, Drosophila; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases