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A positive role for the PP2A catalytic subunit in Wnt signal transduction

M J Ratcliffe1, K Itoh, S Y Sokol

  • 1Department of Microbiology and Molecular Genetics, Harvard Medical School, Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, Massachessetts 02215, USA. mratclif@caregroup.harvard.edu

The Journal of Biological Chemistry
|September 29, 2000
PubMed

Insights

Protein phosphatase-2A (PP2A) positively regulates Wnt signaling by enhancing Dishevelled activity. This enzyme functions downstream of beta-catenin, suggesting PP2A impacts Wnt pathways at multiple levels.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Protein phosphatase-2A (PP2A) is a key enzyme in cellular processes.
  • PP2A subunits interact with Wnt pathway components Axin and Adenomatous Polyposis Coli.
  • The Wnt pathway is crucial for development and gene regulation.

Purpose of the Study:

  • To investigate the role of PP2A in Wnt signal transduction.
  • To determine the specific mechanisms by which PP2A influences Wnt signaling.
  • To elucidate the relationship between PP2A and beta-catenin in the Wnt pathway.

Main Methods:

  • Experiments were conducted using early Xenopus embryos.
  • Assays included secondary axis induction and Siamois reporter gene activation.
  • The effects of PP2A catalytic subunit (PP2A-C), small t antigen, and PP2A-B'epsilon subunit were examined.

Main Results:

  • PP2A-C potentiated Dishevelled-mediated signaling, indicating a positive regulatory role.
  • Inhibition of PP2A-C or its antagonist small t antigen blocked Dishevelled signaling.
  • PP2A-C did not significantly alter beta-catenin stability but affected pathways activated by stabilized beta-catenin, suggesting a downstream role.

Conclusions:

  • PP2A positively regulates Wnt signaling, likely acting downstream of beta-catenin.
  • PP2A may influence the Wnt pathway at multiple regulatory points.
  • These findings expand the understanding of Wnt pathway regulation by PP2A.

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