Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3

@article{Huang2004DifferentialRO,
  title={Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3},
  author={Qiaojia Huang and Jianhua Yang and Yong Loo Lin and Christopher Walker and Jinke Cheng and Zheng-Gang Liu and Bing Su},
  journal={Nature Immunology},
  year={2004},
  volume={5},
  pages={98-103}
}
Interleukin 1 receptor (IL-1R) and Toll-like receptors (TLRs) induce inflammatory genes through the complex of MyD88, IL-1R-associated protein kinase (IRAK) and tumor necrosis factor receptor–associated factor 6 (TRAF6), which is believed to function 'upstream' of the cascades of IκB kinase (IKK) and nuclear factor-κB (NF-κB); extracellular signal-regulated protein kinase (ERK); c-Jun N-terminal kinase (JNK); and p38 mitogen-activated protein kinase (MAPK). Here we show that MAPK–ERK kinase… 

Modulation of Toll–interleukin 1 receptor mediated signaling

Genetic and biochemical studies reveal that IL-1R uses adaptor molecule MyD88 to mediate a very complex pathway, involving a cascade of kinases organized by multiple adapter molecules into signaling complexes, leading to activation of the transcription factor NFκB.

SIGIRR Inhibits Interleukin-1 Receptor- and Toll-like Receptor 4-mediated Signaling through Different Mechanisms*

Results indicate that SIGIRR inhibits IL-1 and LPS signaling pathways through differential mechanisms.

IRAK-4 Kinase Activity Is Required for Interleukin-1 (IL-1) Receptor- and Toll-like Receptor 7-mediated Signaling and Gene Expression*

The results suggest that IRAK-4 kinase activity plays a critical role in IL-1 receptor (IL-1R)/TLR7-mediated induction of inflammatory responses.

CaMKII promotes TLR-triggered proinflammatory cytokine and type I interferon production by directly binding and activating TAK1 and IRF3 in macrophages.

It is demonstrated that TLR 4, 9, and 3 ligands markedly induce intracellular calcium fluxes and activate CaMKII-alpha in macrophages, and in turn promotes both myeloid differentiating factor 88 and Toll/IL-1 receptor domain-containing adaptor protein-inducing IFN-beta-dependent inflammatory responses by directly activating TAK1 and IRF3.

Interleukin-8 Induces Nuclear Transcription Factor-κB through a TRAF6-dependent Pathway*

The data suggest that IL-8-induced NF-κB activation proceeds through a TRAF2-independent but TRAF6-dependent pathway, followed by recruitment of IRAK and activation of IKK andactivation of NF-σκB and its dependent genes may be one of the pathways of IL- 8-induced inflammation and angiogenesis.

Mitogen-activated protein kinase phosphatase-1 (MKP-1): a critical regulator of innate immune responses

Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a nuclear-localized dual-specificity phosphat enzyme that is induced by TLR stimulation in macrophages, resulting in the attenuation of TLR-triggered production of pro-inflammatory cytokines and other inflammatory mediators.

Phosphatidylinositol 4-Phosphate 5-Kinase α Facilitates Toll-like Receptor 4-mediated Microglial Inflammation through Regulation of the Toll/Interleukin-1 Receptor Domain-containing Adaptor Protein (TIRAP) Location*

The results suggest that PIP5Kα promotes TLR4-associated microglial inflammation by mediating PIP2-dependent recruitment of TIRAP to the plasma membrane.

Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFκB Activation Pathways Bifurcate at IL-1 Receptor-associated Kinase Modification*

Through the study of these IRAK modification mutants, two parallel IL-1-mediated signaling pathways for NFκB activation, TAK1-dependent and MEKK3-dependent, respectively are uncovered and provide significant insight to the further understanding of NFκBs activation pathways.
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