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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

Author Affiliations

  1. Ekatherina Serysheva1,2,
  2. Hebist Berhane3,4,
  3. Luca Grumolato5,6,
  4. Kubilay Demir7,
  5. Sophie Balmer1,2,
  6. Maxime Bodak3,4,
  7. Michael Boutros7,
  8. Stuart Aaronson5,
  9. Marek Mlodzik*,1,2 and
  10. Andreas Jenny*,3,4
  1. 1 Department of Developmental and Regenerative Biology, New York, New York, 10029, USA
  2. 2 Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA
  3. 3 Department of Developmental and Molecular Biology, Bronx, New York, USA
  4. 4 Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA
  5. 5 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10461, USA
  6. 6 INSERM U982‐University of Rouen, 76821, Mont Saint Aignan, France
  7. 7 German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, and Heidelberg University, Medical Faculty Mannheim, Department for Cell and Molecular Biology, Im Neuenheimer Feld 580, Heidelberg 69120, Germany
  1. *Corresponding authors. Tel:+1 212 241 6516; Fax:+1 212 241 8610; E-mail: marek.mlodzi{at}mssm.edu or Tel:+1 718 430 4183; Fax:+1 718 430 8567; E-mail: andreas.jenny{at}einstein.yu.edu

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.

  • Received November 30, 2012.
  • Revision received May 29, 2013.
  • Accepted May 31, 2013.

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