論文 - 詳細
| RRC ID | 41950 |
|---|---|
| 著者 | Matsuguchi T, Masuda A, Sugimoto K, Nagai Y, Yoshikai Y. |
| タイトル | JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation. |
| ジャーナル | EMBO J |
| Abstract |
Lipopolysaccharide (LPS) is recognized by Toll-like receptor (TLR) 4 and activates NF-kappaB and a set of MAP kinases. Here we have investigated proteins associated with the cytoplasmic domain of mouse TLR4 by yeast two-hybrid screening and identified JNK-interacting protein 3 (JIP3), a scaffold protein for JNK, as a TLR4-associated protein. In mammalian cells, JIP3, through its N-terminal region, constitutively associates with TLR4. The association is specific to JIP3, as the two other JIPs, JIP1 and JIP2, failed to bind TLR4. In HEK 293 cells exogenously expressing TLR4, MD2 and CD14, co-expression of JIP3 significantly increased the complex formation of TLR4-JNK and LPS-mediated JNK activation. In contrast, expression of C-terminally truncated forms of JIP3 impaired LPS-induced JNK activation in a mouse macrophage cell line, RAW264.7. Moreover, RNA interference of JIP3 inhibited LPS-mediated JNK activation. In RAW264.7 cells, JIP3 associates MEKK-1, but not with TAK-1. Finally, JIP3 also associates with TLR2 and TLR9, but not with TLR1 or TLR6. Altogether, our data indicate the involvement of JIP3 in JNK activation in downstream signals of some TLRs. |
| 巻・号 | 22(17) |
| ページ | 4455-64 |
| 公開日 | 2003-9-1 |
| DOI | 10.1093/emboj/cdg438 |
| PMID | 12941697 |
| PMC | PMC202380 |
| MeSH | Adaptor Proteins, Signal Transducing* Animals Base Sequence Binding Sites Cell Line DNA, Complementary / genetics Enzyme Activation / drug effects JNK Mitogen-Activated Protein Kinases Lipopolysaccharides / toxicity* MAP Kinase Kinase Kinase 1* MAP Kinase Kinase Kinases / metabolism Membrane Glycoproteins / chemistry Membrane Glycoproteins / metabolism* Mice Mitogen-Activated Protein Kinases / metabolism* Models, Biological Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Protein Serine-Threonine Kinases / metabolism Protein Structure, Tertiary RNA Interference Receptors, Cell Surface / chemistry Receptors, Cell Surface / metabolism* Recombinant Proteins / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Sequence Deletion Signal Transduction Toll-Like Receptor 1 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors Transfection Two-Hybrid System Techniques |
| IF | 9.889 |
| 引用数 | 72 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) COS-7(RCB0539) 293(RCB1637) |