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MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm

Kouhei Masuda1, Chiaki Katagiri, Miyuki Nomura

  • 1Miyagi Cancer Center Research Institute, Natori, Japan.

Biochemical and Biophysical Research Communications
|February 4, 2010
PubMed

Insights

Mitogen-activated protein kinase phosphatase-7 (MKP-7) acts as a scaffold protein, prolonging ERK phosphorylation. MKP-7 down-regulates ERK-dependent gene expression by preventing phospho-ERK nuclear accumulation.

Area of Science:

  • Molecular Biology
  • Cell Signaling

Background:

  • Mitogen-activated protein kinase phosphatase-7 (MKP-7) is a JNK-specific phosphatase.
  • MKP-7 also interacts with Extracellular signal-regulated kinase (ERK), and ERK phosphorylation stabilizes MKP-7.

Purpose of the Study:

  • To analyze the function of MKP-7 in the activation of ERK.
  • To investigate the role of MKP-7 in regulating ERK-mediated transcription.

Main Methods:

  • Time-course experiments to assess ERK phosphorylation.
  • Immunohistology to examine phospho-ERK localization.
  • Reporter gene assays to evaluate transcriptional activity.

Main Results:

  • MKP-7 and its phosphatase-dead mutant prolonged mitogen-induced ERK phosphorylation, suggesting a scaffold function.
  • MKP-7 blocked nuclear translocation of phospho-ERK and co-localized with phospho-ERK in the cytoplasm.
  • MKP-7 inhibited ERK-mediated transcription.

Conclusions:

  • MKP-7 functions as a scaffold protein for ERK.
  • MKP-7 down-regulates ERK-dependent gene expression by inhibiting nuclear accumulation of phospho-ERK.

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