Journal ArticleDOI
TRAF6 is a signal transducer for interleukin-1
TLDR
The identification of a new TRAF family member is reported, designated TRAF6, which indicates that TRAF proteins may function as signal transducers for distinct receptor families and that TRAf6 participates in IL-1 signalling.Abstract:
Many cytokines signal through different cell-surface receptors to activate the transcription factor NF-kappaB. Members of the TRAF protein family have been implicated in the activation of NF-kappaB by the tumour-necrosis factor (TNF)-receptor superfamily. Here we report the identification of a new TRAF family member, designated TRAF6. When overexpressed in human 293 cells, TRAF6 activates NF-kappaB. A dominant-negative mutant of TRAF6 inhibits NF-kappaB activation signalled by interleukin-1 (IL-1) but not by TNF. IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction. These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.read more
Citations
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Journal ArticleDOI
Innate Immune Recognition
TL;DR: Microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens to distinguish infectious nonself from noninfectious self.
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NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses
TL;DR: Recently, significant advances have been made in elucidating the details of the pathways through which signals are transmitted to the NF-kappa B:I kappa B complex in the cytosol and their implications for the study of NF-Kappa B.
Journal ArticleDOI
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Michael Karin,Yinon Ben-Neriah +1 more
TL;DR: Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
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Toll-like receptors and innate immunity
TL;DR: This work has shown that activation of inflammatory and antimicrobial innate immune responses through recognition of Toll-like receptors expressed on dendritic cells triggers functional maturation of dendrites and leads to initiation of antigen-specific adaptive immune responses.
Journal ArticleDOI
Signaling to NF-kappaB.
Matthew S. Hayden,Sankar Ghosh +1 more
TL;DR: An overview of established NF-kappaB signaling pathways is provided with focus on the current state of research into the mechanisms that regulate IKK activation and NF- kappaB transcriptional activity.
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Biologic basis for interleukin-1 in disease
TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
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TRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways
TL;DR: It is shown that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively, and these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
Journal ArticleDOI
Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin
TL;DR: How LBP enables LPS binding to CD14 and how complexes of LPS and soluble or GPI-anchored CD14 participate in cell activation are discussed, and the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, is reviewed.
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The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins
TL;DR: The biochemical purification and subsequent molecular cloning of two novel TNFR2-associated proteins, designated c-IAP1 and c- IAP2, that are closely related mammalian members of the inhibitor of apoptosis protein (IAP) family originally identified in baculoviruses are reported.