title: Chemical genetic analysis of the time course of signal transduction by JNK.
abstract: Exposure of primary murine embryonic fibroblasts to tumor necrosis factor (TNF) causes biphasic activation of the c-Jun NH(2)-terminal kinase (JNK) signaling pathway. The early phase (30 min) of the response to TNF is a large and transient increase in JNK activity. This response is followed by a second and more sustained phase of JNK activation that lasts many hours. We employed a chemical genetic strategy to dissect the functional consequences of these two phases of JNK activation. We report that both the early and late phases of JNK activation contribute to TNF-induced gene expression. In contrast, the early transient phase of JNK activation (<1 hr) can signal cell survival, while the later and more sustained phase of JNK activation (1-6 hr) can mediate proapoptotic signaling. These data indicate that the time course of JNK signaling can influence the biological response to JNK activation.
authors.affiliation: Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, USA.
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Ventura
authors.forename: Anette
authors.initials: A
authors.lastname: Hübner
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases