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Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis

Kunio Kondoh1, Kazunori Sunadome, Eisuke Nishida

  • 1Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.

The Journal of Biological Chemistry
|December 13, 2006
PubMed

Insights

Notch signaling suppresses muscle development by inducing MKP-1, which inhibits p38 MAPK activity. This discovery reveals a new cross-talk mechanism between Notch and p38 pathways crucial for cell fate regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Intracellular signaling pathways regulate cell fate and responses.
  • Notch and MAPK pathways are critical in biological processes.
  • Notch interacts with ERK-MAPK, but interactions with other MAPKs are unknown.

Purpose of the Study:

  • Investigate the interaction between Notch signaling and p38 MAPK.
  • Determine the role of this interaction in C2C12 myogenesis.

Main Methods:

  • Utilized C2C12 cell line for experiments.
  • Analyzed Notch signaling activation and p38 MAPK activity.
  • Measured expression of dual-specificity MAPK phosphatase (MKP-1).
  • Employed short interfering RNA (siRNA) to inhibit MKP-1.

Main Results:

  • Notch signaling activation suppressed p38 MAPK activity in C2C12 cells.
  • Notch specifically induced MKP-1 expression, which inactivates p38.
  • MKP-1 induction by Notch depends on RBP-J.
  • MKP-1 inhibition partially rescued the negative regulation of myogenesis.

Conclusions:

  • Notch signaling negatively regulates C2C12 myogenesis via p38 MAPK inhibition.
  • Notch induces MKP-1 expression in an RBP-J-dependent manner.
  • A novel cross-talk between Notch and p38 MAPK pathways, mediated by MKP-1, is identified.

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