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MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

C Tournier1, C Dong, T K Turner

  • 1Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Genes & Development
|June 8, 2001
PubMed

Insights

Mitogen-activated protein kinase (MAPK) pathways involving MKK4 and MKK7 kinases play distinct roles in cellular stress responses. Simultaneous gene disruption blocked environmental stress-induced JNK activation, while MKK7 disruption alone inhibited cytokine-induced JNK activation.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Stress response mechanisms

Background:

  • Mitogen-activated protein kinases (MAPKs) are crucial signaling molecules.
  • MAPKs are activated by phosphorylation by MAPK kinases (MKKs).
  • The c-Jun NH(2)-terminal kinase (JNK) group of MAPKs is activated by MKK4 and MKK7.

Purpose of the Study:

  • To investigate the in vivo roles of MKK4 and MKK7 in JNK activation.
  • To differentiate the functions of MKK4 and MKK7 in response to various stimuli.

Main Methods:

  • Gene targeting in mice to disrupt Mkk4 and Mkk7 genes.
  • Analysis of JNK activation in response to environmental stress and proinflammatory cytokines.

Main Results:

  • Simultaneous disruption of Mkk4 and Mkk7 was necessary to inhibit JNK activation induced by environmental stress.
  • Disruption of Mkk7 alone was sufficient to prevent JNK activation induced by proinflammatory cytokines.
  • MKK4 and MKK7 exhibit distinct functions in JNK signaling.

Conclusions:

  • MKK4 and MKK7 play non-redundant roles in the JNK signal transduction pathway.
  • The specific MKK kinase determines the JNK activation pathway in response to different cellular stimuli.

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