RRC ID 77013
Author Okada M, Matsuzawa A, Yoshimura A, Ichijo H.
Title The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation.
Journal 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.
Volume 289(47)
Pages 32926-36
Published 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
Human and Animal Cells THP-1(RCB1189)