Chemical genetic analysis of the time course of signal transduction by JNK

Molecular Cell
Juan-Jose VenturaRoger J Davis

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.

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Citations

Jul 24, 2010·Molecules and Cells·Michael J Morgan, Zheng-Gang Liu
Jun 14, 2013·Apoptosis : an International Journal on Programmed Cell Death·Jing YangAkihito Yokoyama
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