Chemical genetic analysis of the time course of signal transduction by JNK
Chemical genetic analysis of the time course of signal transduction by JNK
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DOI：
10.1016/j.molcel.2006.01.018
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发表时间：
2006-03-03
期刊：
影响因子：
16
通讯作者：
Davis, RJ
中科院分区：
文献类型：
--
作者：
Ventura, JJ;H端bner, A;Davis, RJ
原代小鼠胚胎成纤维细胞暴露于肿瘤坏死因子 (TNF) 会导致 c-Jun NH2 末端激酶 (JNK) 信号通路的双相激活。 TNF 反应的早期阶段（30 分钟）是 JNK 活性大幅且短暂的增加。此反应之后是 JNK 激活的第二个且更持续的阶段，持续数小时。我们采用化学遗传策略来剖析 JNK 激活这两个阶段的功能后果。我们报告 JNK 激活的早期和晚期均有助于 TNF 包含的基因表达。相反，JNK 激活的早期瞬时阶段（< 1 小时）可以发出细胞存活信号，而 JNK 激活的较晚且更持续的阶段（1-6 小时）可以介导促凋亡信号传导。这些数据表明 JNK 信号传导的时间进程可以影响对 JNK 激活的生物反应。
Exposure of primary murine embryonic fibroblasts to tumor necrosis factor (TNF) causes biphasic activation of the c-Jun NH2-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-incluced 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.