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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK

Claire Letourneux1, Géraldine Rocher, Françoise Porteu

  • 1Department of Hematology, Institut Cochin, INSERM U567, Paris, France.

The EMBO Journal
|February 4, 2006
PubMed

Insights

Protein phosphatase 2A (PP2A) B56 holoenzymes dephosphorylate extracellular signal-regulated kinase (ERK). IEX-1 protein inhibits B56-PP2A activity during mitogenic stimulation, revealing a novel regulatory mechanism in ERK signaling.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Protein phosphatase 2A (PP2A) is crucial in regulating cellular processes.
  • The extracellular signal-regulated kinase (ERK) pathway controls cell growth and differentiation.
  • The specific PP2A holoenzymes involved in ERK dephosphorylation and their regulation remain unclear.

Purpose of the Study:

  • To investigate the role of specific PP2A B regulatory subunits in ERK dephosphorylation.
  • To determine how mitogenic stimulation affects PP2A-mediated ERK dephosphorylation.
  • To elucidate the mechanism by which IEX-1 regulates B56-PP2A activity.

Main Methods:

  • RNA interference and overexpression of PP2A B regulatory subunits.
  • Analysis of ERK dephosphorylation and activation by MEK.
  • Investigation of IEX-1 binding to B56 subunits and phosphorylated ERK (pERK).
  • Assessment of B56 phosphorylation and dissociation from the catalytic subunit.

Main Results:

  • B56 family members of PP2A enhance ERK dephosphorylation, independent of MEK activation.
  • Mitogenic stimulation induces IEX-1, which reverses B56-PP2A-mediated ERK dephosphorylation.
  • IEX-1 binds to B56 and pERK, promoting B56 phosphorylation by ERK and dissociation from the catalytic subunit.
  • This study identifies a novel B56-specific inhibitor of PP2A activity.

Conclusions:

  • B56-containing PP2A holoenzymes are key players in ERK dephosphorylation.
  • IEX-1 acts as an ERK-dependent inhibitor of B56-PP2A activity during mitogenic stimulation.
  • A new paradigm in ERK signaling is proposed, involving transphosphorylation of associated proteins by ERK.

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