Wg/Wnt signal can be transmitted through arrow/LRP5,6 and axin independently of Zw3/Gsk3β activity

Nicholas S. Tolwinski, Marcel Wehrli, Anna Rives, Naz Erdeniz, Stephen DiNardo, Eric Wieschaus

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3β/Zw3, the kinase normally required for controlling β-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.

Original languageEnglish (US)
Pages (from-to)407-418
Number of pages12
JournalDevelopmental Cell
Volume4
Issue number3
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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