The human toll signaling pathway: Divergence of nuclear factor κb and jnk/sapk activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)

Marta Muzio, Gioacchino Natoli, Simona Saccani, Massimo Levrero, Alberto Mantovani

Research output: Contribution to journalArticle

509 Citations (Scopus)

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 κB (NF-κB)-inducing kinase (NIK) are both involved in subsequent steps of NF-κB 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.

Original languageEnglish
Pages (from-to)2097-2101
Number of pages5
JournalJournal of Experimental Medicine
Volume187
Issue number12
DOIs
Publication statusPublished - Jun 15 1998

Fingerprint

Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Drosophila
Phosphotransferases
Interleukin-1 Receptors
JNK Mitogen-Activated Protein Kinases
Tumor Necrosis Factor Receptors
Adaptive Immunity
Heat-Shock Proteins
Protein Kinases

Keywords

  • C-Jun NH-terminal kinase/stress-activated protein kinase
  • Interleukin 1 receptor
  • Nuclear factor κB
  • Toll

ASJC Scopus subject areas

  • Immunology

Cite this

@article{cc14663905924dc49586e334af4de57d,
title = "The human toll signaling pathway: Divergence of nuclear factor κb and jnk/sapk activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)",
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 κB (NF-κB)-inducing kinase (NIK) are both involved in subsequent steps of NF-κB 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.",
keywords = "C-Jun NH-terminal kinase/stress-activated protein kinase, Interleukin 1 receptor, Nuclear factor κB, Toll",
author = "Marta Muzio and Gioacchino Natoli and Simona Saccani and Massimo Levrero and Alberto Mantovani",
year = "1998",
month = "6",
day = "15",
doi = "10.1084/jem.187.12.2097",
language = "English",
volume = "187",
pages = "2097--2101",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

TY - JOUR

T1 - The human toll signaling pathway

T2 - Divergence of nuclear factor κb and jnk/sapk activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)

AU - Muzio, Marta

AU - Natoli, Gioacchino

AU - Saccani, Simona

AU - Levrero, Massimo

AU - Mantovani, Alberto

PY - 1998/6/15

Y1 - 1998/6/15

N2 - 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 κB (NF-κB)-inducing kinase (NIK) are both involved in subsequent steps of NF-κB 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.

AB - 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 κB (NF-κB)-inducing kinase (NIK) are both involved in subsequent steps of NF-κB 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.

KW - C-Jun NH-terminal kinase/stress-activated protein kinase

KW - Interleukin 1 receptor

KW - Nuclear factor κB

KW - Toll

UR - http://www.scopus.com/inward/record.url?scp=0032526861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032526861&partnerID=8YFLogxK

U2 - 10.1084/jem.187.12.2097

DO - 10.1084/jem.187.12.2097

M3 - Article

C2 - 9625770

AN - SCOPUS:0032526861

VL - 187

SP - 2097

EP - 2101

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 12

ER -