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Updated: Apr 27, 2026

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c-Myb negatively regulates Ras signaling through induction of dual phosphatase MKP-3 in NIH3T3 cells

Young Jae Park1, Jong Min Lee2, Mi So Lee2

  • 1School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.

Biochemical and Biophysical Research Communications
|July 1, 2014
PubMed

Insights

Ras signaling activates Mitogen-activated protein kinase phosphatase-3 (MKP-3) gene expression through the transcription factor c-Myb. This study reveals a novel c-Myb-dependent mechanism regulating MKP-3 in response to Ras activation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Mitogen-activated protein kinase phosphatase-3 (MKP-3) is a key negative regulator of the ERK1/2 MAPK pathway.
  • The precise molecular mechanisms by which Ras signaling influences MKP-3 expression remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular mechanism underlying Ras-induced transcriptional activation of the MKP-3 gene.
  • To identify the transcription factors involved in this regulatory process.

Main Methods:

  • Analysis of MKP-3 mRNA levels following H-Ras expression.
  • Reporter assays using MKP-3 promoter deletion constructs.
  • Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) to assess c-Myb binding.
  • siRNA-mediated knockdown of c-Myb.

Main Results:

  • Constitutively active H-Ras expression increased MKP-3 mRNA levels.
  • A specific c-Myb binding site within the MKP-3 promoter was essential for Ras-induced transcriptional activity.
  • c-Myb was shown to directly bind to the MKP-3 promoter.
  • Knockdown of c-Myb abolished Ras-induced MKP-3 promoter activity.

Conclusions:

  • Ras signaling activates c-Myb-dependent transcription of the MKP-3 gene.
  • This study elucidates a novel regulatory pathway involving Ras, c-Myb, and MKP-3.
  • Findings provide new insights into the intricate feedback mechanisms controlling MAPK signaling.
Keywords:
ERKH-RasMKP-3NIH3T3 fibroblastsc-Myb

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