Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling

Ekatherina Serysheva, Hebist Berhane, Luca Grumolato, Kubilay Demir, Sophie Balmer, Maxime Bodak, Michael Boutros, Stuart Aaronson, Marek Mlodzik, Andreas Jenny

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Wnt/β-catenin signalling is central to development and its regulation is essential in preventing cancer. Using phosphorylation of Dishevelled as readout of pathway activation, we identified Drosophila Wnk kinase as a new regulator of canonical Wnt/β-catenin signalling. WNK kinases are known for regulating ion co-transporters associated with hypertension disorders. We demonstrate that wnk loss-of-function phenotypes resemble canonical Wnt pathway mutants, while Wnk overexpression causes gain-of-function canonical Wnt-signalling phenotypes. Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a conserved function in ensuring peak levels of canonical Wnt signalling.

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalEMBO Reports
Volume14
Issue number8
DOIs
StatePublished - Aug 2013

Keywords

  • Dishevelled
  • Drosophila
  • Gordon syndrome
  • Wnk kinase
  • Wnt signalling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Serysheva, E., Berhane, H., Grumolato, L., Demir, K., Balmer, S., Bodak, M., Boutros, M., Aaronson, S., Mlodzik, M., & Jenny, A. (2013). Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. EMBO Reports, 14(8), 718-725. https://doi.org/10.1038/embor.2013.88