論文 - 詳細
| RRC ID | 77013 |
|---|---|
| 著者 | Okada M, Matsuzawa A, Yoshimura A, Ichijo H. |
| タイトル | The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation. |
| ジャーナル | J Biol Chem |
| Abstract |
Lysosome rupture triggers NLRP3 inflammasome activation in macrophages. However, the underlying mechanism is not fully understood. Here we showed that the TAK1-JNK pathway, a MAPK signaling pathway, is activated through lysosome rupture and that this activation is necessary for the complete activation of the NLRP3 inflammasome through the oligomerization of an adapter protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). We also revealed that the activation of the TAK1-JNK pathway is sustained through Ca(2+) ions and that calcium/calmodulin-dependent protein kinase type II functions upstream of the TAK1-JNK pathway and specifically regulates lysosome rupture-induced NLRP3 inflammasome activation. These data suggest a novel role for the TAK1-JNK pathway as a critical regulator of NLRP3 inflammasome activation. |
| 巻・号 | 289(47) |
| ページ | 32926-36 |
| 公開日 | 2014-11-21 |
| DOI | 10.1074/jbc.M114.579961 |
| PII | S0021-9258(20)47490-3 |
| PMID | 25288801 |
| PMC | PMC4239639 |
| MeSH | CARD Signaling Adaptor Proteins Calcium / metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line, Tumor Cytoskeletal Proteins / chemistry Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Enzyme Activation HEK293 Cells Humans Immunoblotting Inflammasomes / metabolism* JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* Lysosomes / metabolism* MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* MAP Kinase Signaling System* Microscopy, Fluorescence NLR Family, Pyrin Domain-Containing 3 Protein Protein Multimerization RNA Interference |
| IF | 4.238 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |