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Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells

Tanya Pike1, Charlotte Widberg, Andrew Goodall

  • 1The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Cellular Signalling
|March 26, 2013
PubMed

Insights

A novel truncated form of MEK1 (tMEK) acts as a feedback inhibitor in the MAP kinase pathway. This tMEK dampens ERK and p90RSK activation during G2/M phase, regulating cell cycle progression.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Signal Transduction

Background:

  • The canonical Raf-MEK-ERK MAP kinase cascade is crucial for cellular responses.
  • ERK activation is a primary endpoint, but its regulation, especially during cell cycle phases like G2, is complex.

Purpose of the Study:

  • To investigate a novel signaling outcome of the MAP kinase pathway during G2 phase.
  • To elucidate the role of truncated MEK1 (tMEK) in regulating MAP kinase signaling and cell cycle progression.

Main Methods:

  • Stimulation of MAP kinase pathway using growth factors or phorbol esters during G2 phase.
  • Analysis of ERK and p90RSK activation dynamics.
  • Expression and functional analysis of recombinant MEK1 mutants, including catalytically inactive and phosphorylated forms.
  • Assessment of tMEK accumulation and its impact on signaling and mitosis.

Main Results:

  • MAP kinase pathway activation in G2 phase leads to transient ERK and p90RSK activation followed by suppression.
  • A novel truncated form of MEK1 (tMEK) is induced upon G2 phase MAP kinase activation.
  • Catalytically inactive but phosphorylated tMEK mutants inhibit ERK and p90RSK activation and delay mitosis.
  • Lack of MEK1 or tMEK accumulation abrogates feedback inhibition of ERK and p90RSK.

Conclusions:

  • tMEK is a novel output of the MAP kinase pathway, functioning as a negative feedback regulator.
  • tMEK dampens the magnitude and duration of MAP kinase signaling during G2/M phase.
  • This mechanism plays a role in controlling cell cycle progression by modulating ERK and p90RSK activity.

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