Toll-like receptor 2–mediated NF-κB activation requires a Rac1-dependent pathway
| Autor: | Nicole Teusch, Mausumee Guha, Lois Kline, Jean Paul Mira, Paul J. Godowski, Nigel Mackman, Laurence Arbibe, Richard J. Ulevitch, Ulla G. Knaus |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
rac1 GTP-Binding Protein
Staphylococcus aureus Cell signaling Immunology Gene Expression Receptors Cell Surface Protein Serine-Threonine Kinases Biology Transfection Models Biological Cell Line Phosphatidylinositol 3-Kinases chemistry.chemical_compound Transactivation Proto-Oncogene Proteins Drosophila Proteins Humans Immunology and Allergy Phosphotyrosine cdc42 GTP-Binding Protein Protein kinase B PI3K/AKT/mTOR pathway Toll-like receptor Membrane Glycoproteins Toll-Like Receptors NF-kappa B Tyrosine phosphorylation Toll-Like Receptor 2 Cell biology TLR2 IκBα chemistry Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Nature Immunology. 1:533-540 |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | 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-kappa B (NF-kappa B) 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-kappa B transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of I kappa B alpha degradation. Thus Rac1 controls a second, I kappa B-independent, pathway to NF-kappa B activation and is essential in innate immune cell signaling via TLR2. |
| Databáze: | OpenAIRE |
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