The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).
The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent steps of NF-kappaB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.
Muzio
M
M
Department of Immunology and Cell Biology, Mario Negri Institute, I-20157 Milan, Italy. muziom@irfmn.mnegri.it
Natoli
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G
Saccani
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Levrero
M
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Mantovani
A
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases