RRC ID 56704
著者 Miura H, Kondo Y, Matsuda M, Aoki K.
タイトル Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death.
ジャーナル Cell Rep
Abstract The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are important players in cell-fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in inflammatory and stress responses. However, it is unknown how this crosstalk affects signaling dynamics, cell-to-cell variation, and cellular responses at the single-cell level. We established a multiplexed live-cell imaging system based on kinase translocation reporters to simultaneously monitor JNK and p38 activities with high specificity and sensitivity at single-cell resolution. Various stresses activated JNK and p38 with various dynamics. In all cases, p38 suppressed JNK activity in a cross-inhibitory manner. We demonstrate that p38 antagonizes JNK through both transcriptional and post-translational mechanisms. This cross-inhibition generates cellular heterogeneity in JNK activity after stress exposure. Our data indicate that this heterogeneity in JNK activity plays a role in fractional killing in response to UV stress.
巻・号 24(10)
ページ 2658-2668
公開日 2018-9-4
DOI 10.1016/j.celrep.2018.08.020
PII S2211-1247(18)31274-9
PMID 30184500
MeSH Apoptosis / radiation effects Cell Death / physiology Cell Death / radiation effects Dual Specificity Phosphatase 1 / genetics Dual Specificity Phosphatase 1 / metabolism Humans JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Signaling System / radiation effects Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism Optical Imaging Signal Transduction / genetics Signal Transduction / physiology Ultraviolet Rays p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism*
IF 7.815
引用数 9
リソース情報
遺伝子材料 CSII-EF-MCS (RDB04378) pCMV-VSV-G-RSV-Rev (RDB04393)