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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Survival / physiology
  • Cells, Cultured
  • Fibroblasts / physiology
  • Gene Expression Regulation / physiology
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • Mice
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / physiology


  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases