Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death.
Cell Rep
; 24(10): 2658-2668, 2018 09 04.
Article
de En
| MEDLINE
| ID: mdl-30184500
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
JNK Mitogen-Activated Protein Kinases
/
P38 Mitogen-Activated Protein Kinases
Type d'étude:
Etiology_studies
Limites:
Humans
Langue:
En
Journal:
Cell Rep
Année:
2018
Type de document:
Article