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

doi:10.1038/embor.2013.88

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

Developmental & Molecular Biology

Research output: Contribution to journal › Article › peer-review

37 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 language	English (US)
Pages (from-to)	718-725
Number of pages	8
Journal	EMBO Reports
Volume	14
Issue number	8
DOIs	https://doi.org/10.1038/embor.2013.88
State	Published - Aug 2013

Keywords

Dishevelled
Drosophila
Gordon syndrome
Wnk kinase
Wnt signalling

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/embor.2013.88

Cite this

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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.",

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AU - Serysheva, Ekatherina

AU - Berhane, Hebist

AU - Grumolato, Luca

AU - Demir, Kubilay

AU - Balmer, Sophie

AU - Bodak, Maxime

AU - Boutros, Michael

AU - Aaronson, Stuart

AU - Mlodzik, Marek

AU - Jenny, Andreas

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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