Chemical Genetic Analysis of the Time Course of Signal Transduction by JNK

• DOI: 10.1016/j.molcel.2006.01.018
• Publication Date: 2006-03-03T12:34:11Z
• Authors: Juan-Jose Ventura; Anette Hübner; Chao Zhang; Richard A. Flavell; Kevan M. Shokat; Roger J. Davis
• Keywords: Course (navigation)

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.