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PMID: 9625770 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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 Journal of experimental medicine ·Vol. 187 ·No. 12 ·1998-06-15 ·Pages 2097-101

Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Antigens, Differentiation Calcium-Calmodulin-Dependent Protein Kinases/metabolism Humans JNK Mitogen-Activated Protein Kinases Membrane Glycoproteins Membrane Proteins/metabolism Mitogen-Activated Protein Kinases Models, Immunological Molecular Sequence Data Monocytes/immunology Myeloid Differentiation Factor 88 NF-kappa B/metabolism Proteins/metabolism Receptors, Cell Surface Receptors, Immunologic/metabolism Receptors, Tumor Necrosis Factor/metabolism Sequence Homology, Amino Acid Signal Transduction TNF Receptor-Associated Factor 6 Toll-Like Receptors
Chemicals
Adaptor Proteins, Signal Transducing Antigens, Differentiation MYD88 protein, human Membrane Glycoproteins Membrane Proteins Myeloid Differentiation Factor 88 NF-kappa B Proteins Receptors, Cell Surface Receptors, Immunologic Receptors, Tumor Necrosis Factor TNF Receptor-Associated Factor 6 Toll-Like Receptors Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Muzio M
Department of Immunology and Cell Biology, Mario Negri Institute, I-20157 Milan, Italy. muziom@irfmn.mnegri.it
Natoli G
Saccani S
Levrero M
Mantovani A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.187.12.2097
Email
muziom@irfmn.mnegri.it
Published
1998-06-15
Pages
2097-101
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212359
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.187.12.2097 PMC Full Text View journal details
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