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
BiologyInterleukin-1 receptorCell biologyKinaseSignal transductionTumor necrosis factor alphaToll-like receptorReceptorCancer researchMolecular biologyImmunologyCytokineInnate immune systemInterleukinGenetics
MeSH Terms
Adaptor ProteinsSignal TransducingAmino Acid SequenceAntigensDifferentiationCalcium-Calmodulin-Dependent Protein KinasesHumansJNK Mitogen-Activated Protein KinasesMembrane GlycoproteinsMembrane ProteinsMitogen-Activated Protein KinasesModelsImmunologicalMolecular Sequence DataMonocytesMyeloid Differentiation Factor 88NF-kappa BProteinsReceptorsCell SurfaceReceptorsImmunologicReceptorsTumor Necrosis FactorSequence HomologyAmino AcidSignal TransductionTNF Receptor-Associated Factor 6Toll-Like Receptors
Affiliated Institutions
Related Publications
Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span
Abstract Neutrophil responses to commercial LPS, a dual Toll-like receptor (TLR)2 and TLR4 activator, are regulated by TLR expression, but are amplified by contaminating monocyt...
Peroxisome Proliferator-activated Receptor α Negatively Regulates the Vascular Inflammatory Gene Response by Negative Cross-talk with Transcription Factors NF-κB and AP-1
Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome pr...
Control of Inflammation, Cytokine Expression, and Germinal Center Formation by BCL-6
The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocardit...
Big Mitogen-activated Protein Kinase 1 (BMK1) Is a Redox-sensitive Kinase
Mitogen-activated protein (MAP) kinases are a multigene family activated by many extracellular stimuli. There are three groups of MAP kinases based on their dual phosphorylation...
Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe
Abstract Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common...
Publication Info
- Year
- 1998
- Type
- article
- Volume
- 187
- Issue
- 12
- Pages
- 2097-2101
- Citations
- 571
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
571
OpenAlex
24
Influential
467
CrossRef
Cite This
Marta Muzio,
Gioacchino Natoli,
Simona Saccani
et al.
(1998).
The Human Toll Signaling Pathway: Divergence of Nuclear Factor κB and JNK/SAPK Activation Upstream of Tumor Necrosis Factor Receptor–associated Factor 6 (TRAF6).
The Journal of Experimental Medicine
, 187
(12)
, 2097-2101.
https://doi.org/10.1084/jem.187.12.2097
Identifiers
- DOI
- 10.1084/jem.187.12.2097
- PMID
- 9625770
- PMCID
- PMC2212359