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

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

42 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
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

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10.1038/embor.2013.88

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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

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