Journal ArticleDOI
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
Laurence Arbibe,Jean Paul Mira,Jean Paul Mira,Nicole Teusch,Lois Kline,Mausumee Guha,Nigel Mackman,Paul J. Godowski,Richard J. Ulevitch,Ulla G. Knaus +9 more
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TLDR
TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2, and Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR 2.Abstract:
Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-κB (NF-κB) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-κB transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of IκBα degradation. Thus Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR2.read more
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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.
Journal ArticleDOI
Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Journal ArticleDOI
Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
Journal ArticleDOI
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
The complexity of NF-κB signaling in inflammation and cancer
TL;DR: An overview of the most relevant modes of crosstalk and cooperativity between NF-κB and other signaling molecules during inflammation and cancer is provided.
References
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Journal ArticleDOI
The Toll-receptor family and control of innate immunity.
Elizabeth Kopp,Ruslan Medzhitov +1 more
TL;DR: Toll receptors and the associated signaling pathways of nuclear factor kappaB may represent the most ancient host defense system found in mammals, insects and plants.
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Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-κB
Lee V. Madrid,Cun-Yu Wang,Denis C. Guttridge,Arndt J.G. Schottelius,Albert S. Baldwin,Marty W. Mayo +5 more
TL;DR: This work demonstrates that, unlike activated Ras, which can stimulate parallel pathways to activate both DNA binding and the transcriptional activity of NF-κB, Akt stimulates NF-kkB predominantly by upregulating of the transactivation potential of p65.
Journal ArticleDOI
Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85α
David A. Fruman,Scott B. Snapper,Claudine M. Yballe,Laurie Davidson,Jonathan Y. Yu,Frederick W. Alt,Lewis C. Cantley +6 more
TL;DR: Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system and the mouse gene encoding the PI3K adapter subunit p85alpha and its splice variants p55alpha and p50alpha was disrupted.
Journal ArticleDOI
Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2.
TL;DR: The results suggest that Rac 2 is a regulatory component of the human neutrophil NADPH oxidase, and provide new insights into the mechanism by which this oxygen radical-generating system is regulated.
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Activation of Phosphatidylinositol 3-Kinase in Response to Interleukin-1 Leads to Phosphorylation and Activation of the NF-κB p65/RelA Subunit
TL;DR: It is found that IL-1 stimulates the PI3K-dependent phosphorylation and transactivation of NF-κB, a process quite distinct from the liberation of NF -κB from its cytoplasmic inhibitor IκB.