論文 - 詳細
| RRC ID | 1966 |
|---|---|
| 著者 | Aki D, Mashima R, Saeki K, Minoda Y, Yamauchi M, Yoshimura A. |
| タイトル | Modulation of TLR signalling by the C-terminal Src kinase (Csk) in macrophages. |
| ジャーナル | Genes Cells |
| Abstract |
In macrophages and monocytes, lipopolysaccharide (LPS) triggers the production of pro-inflammatory cytokine through Toll-like receptor (TLR) 4. Although major TLR signalling pathways are mediated by serine or threonine kinases including IKK, TAK1, p38 and JNKs, a number of reports suggested that tyrosine phosphorylation of intracellular proteins is involved in LPS signalling. Here, we identified several tyrosine-phosphorylated proteins using mass spectrometric analysis in response to LPS stimulation. Among these proteins, we characterized C-terminal Src kinase (Csk), which negatively regulates Src-like kinases in RAW 264.7 cells using RNAi knockdown technology. Unexpectedly, LPS-induced CD40 activation and the secretion of pro-inflammatory cytokine such as IL-6 and TNF-alpha, was down-regulated in Csk knockdown cells. Furthermore, overall cellular tyrosine phosphorylation and TLR4-mediated activation of IkappaB-alpha, Erk and p38 but not of JNK, were also down-regulated in Csk knockdown cells. The protein expression levels of a tyrosine kinase, Fgr, were reduced in Csk knockdown cells, suggesting that Csk is a critical regulator of TLR4-mediated signalling by modifying the levels of Src-like kinases. |
| 巻・号 | 10(4) |
| ページ | 357-68 |
| 公開日 | 2005-4-1 |
| DOI | 10.1111/j.1365-2443.2005.00839.x |
| PII | GTC839 |
| PMID | 15773898 |
| MeSH | Animals CD40 Antigens / metabolism CSK Tyrosine-Protein Kinase Cell Line Chromatography, Liquid DNA-Binding Proteins / metabolism Down-Regulation Interleukin-6 / biosynthesis Lipopolysaccharides / pharmacology Macrophages / metabolism* Mass Spectrometry Mice Phosphorylation Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Receptors, Immunologic / metabolism Receptors, Immunologic / physiology* STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction* Toll-Like Receptor 4 Trans-Activators / metabolism Tumor Necrosis Factor-alpha / metabolism Tyrosine / metabolism* src-Family Kinases |
| IF | 1.655 |
| 引用数 | 32 |
| WOS 分野 | GENETICS & HEREDITY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |