Ventura Juan-Jose, Hübner Anette, Zhang Chao, Flavell Richard A, Shokat Kevan M, Davis Roger J
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, USA.
Mol Cell. 2006 Mar 3;21(5):701-10. doi: 10.1016/j.molcel.2006.01.018.
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.
将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氨基末端激酶（JNK）信号通路的双相激活。对TNF反应的早期阶段（30分钟）是JNK活性的大幅短暂增加。此反应之后是JNK激活的第二个且更持久的阶段，持续数小时。我们采用化学遗传学策略来剖析JNK激活这两个阶段的功能后果。我们报告称，JNK激活的早期和晚期阶段均有助于TNF诱导的基因表达。相比之下，JNK激活的早期短暂阶段（<1小时）可发出细胞存活信号，而JNK激活的后期且更持久阶段（1 - 6小时）可介导促凋亡信号。这些数据表明，JNK信号传导的时间进程可影响对JNK激活的生物学反应。
