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Wnt5a/Ror2-induced upregulation of xPAPC requires xShcA

Ann Caroline Feike1, Klara Rachor, Marc Gentzel

  • 1University Erlangen-Nuremberg, Biology Dept., Developmental Biology Unit, Staudtstr. 5, D-91058 Erlangen, Germany.

Biochemical and Biophysical Research Communications
|August 25, 2010
PubMed

Insights

The Wnt-5a/Ror2 pathway uses ShcA to regulate xPAPC expression in Xenopus development. This identifies ShcA as a key intracellular binding partner in this Wnt-signaling cascade.

Area of Science:

  • Cellular signaling
  • Developmental biology
  • Molecular interactions

Background:

  • Receptor-tyrosine kinases (RTKs) like Ror are crucial in Wnt signaling.
  • Wnt-5a/Ror2 pathways mediate beta-catenin independent signaling.
  • xPAPC expression in Xenopus is linked to Wnt-5a/Ror2 signaling.

Purpose of the Study:

  • To identify intracellular binding partners of Ror2.
  • To elucidate the role of these partners in Wnt-5a/Ror2 signaling.
  • To confirm the functional relevance of the interaction in embryonic development.

Main Methods:

  • Co-immunoprecipitation to identify binding partners.
  • Analysis of protein localization upon Wnt-5a stimulation.
  • Gene knockdown experiments in Xenopus embryos.

Main Results:

  • ShcA, a phospho-tyrosine binding protein, was identified as an Ror2 binding partner.
  • ShcA binds to Ror2 via its SH2-domain at a conserved motif.
  • Wnt-5a induces Ror2 clustering and ShcA recruitment, and ShcA is essential for Wnt-5a/Ror2-mediated xPAPC upregulation.

Conclusions:

  • ShcA acts as an intracellular mediator for the Wnt-5a/Ror2 pathway.
  • The Ror2-ShcA interaction is critical for regulating xPAPC expression during Xenopus development.
  • This study reveals a novel component in beta-catenin independent Wnt signaling.

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