論文 - 詳細
| RRC ID | 39608 |
|---|---|
| 著者 | Kawasaki K, Akashi S, Shimazu R, Yoshida T, Miyake K, Nishijima M. |
| タイトル | Mouse toll-like receptor 4.MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. |
| ジャーナル | J Biol Chem |
| Abstract |
Taxol, an antitumor agent derived from a plant, mimics the action of lipopolysaccharide (LPS) in mice but not in humans. Although Taxol is structurally unrelated to LPS, Taxol and LPS are presumed to share a receptor or signaling molecule. The LPS-mimetic activity of Taxol is not observed in LPS-hyporesponsive C3H/HeJ mice, which possess a point mutation in Toll-like receptor 4 (TLR4); therefore, TLR4 appears to be involved in both Taxol and LPS signaling. In addition, TLR4 was recently shown to physically associate with MD-2, a molecule that confers LPS responsiveness on TLR4. To determine whether TLR4.MD-2 complex mediates a Taxol-induced signal, we constructed transformants of the mouse pro-B cell line, Ba/F3, expressing mouse TLR4 alone, both mouse TLR4 and mouse MD-2, and both mouse MD-2 and mouse TLR4 lacking the cytoplasmic portion, and then examined whether Taxol induced NFkappaB activation in these transfectants. Noticeable NFkappaB activation by Taxol was detected in Ba/F3 expressing mouse TLR4 and mouse MD-2 but not in the other transfectants. Coexpression of human TLR4 and human MD-2 did not confer Taxol responsiveness on Ba/F3 cells, suggesting that the TLR4. MD-2 complex is responsible for the species specificity with respect to Taxol responsiveness. Furthermore, Taxol-induced NFkappaB activation via TLR4.MD-2 was blocked by an LPS antagonist that blocks LPS-induced NFkappaB activation via TLR4.MD-2. These results demonstrated that coexpression of mouse TLR4 and mouse MD-2 is required for Taxol responsiveness and that the TLR4.MD-2 complex is the shared molecule in Taxol and LPS signal transduction in mice. |
| 巻・号 | 275(4) |
| ページ | 2251-4 |
| 公開日 | 2000-1-28 |
| DOI | 10.1074/jbc.275.4.2251 |
| PII | S0021-9258(18)30965-7 |
| PMID | 10644670 |
| MeSH | Animals Blood Drosophila Proteins* Humans Lipopolysaccharides / antagonists & inhibitors Lipopolysaccharides / metabolism* Membrane Glycoproteins / physiology* Mice Mice, Inbred C3H Molecular Mimicry NF-kappa B / metabolism Paclitaxel / metabolism* Paclitaxel / pharmacology Receptors, Cell Surface / physiology* Signal Transduction / drug effects Signal Transduction / physiology* Toll-Like Receptor 4 Toll-Like Receptors |
| IF | 4.238 |
| 引用数 | 277 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Ba/F3(RCB0805) |