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

20 Citations (Scopus)

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

Fingerprint

Catenins
Phosphotransferases
Symporters
Phenotype
Wnt Signaling Pathway
Drosophila
Cell Culture Techniques
Phosphorylation
Ions
Hypertension
Cell culture
Chemical activation
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Cite this

Serysheva, E., Berhane, H., Grumolato, L., Demir, K., Balmer, S., Bodak, 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

Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. / Serysheva, Ekatherina; Berhane, Hebist; Grumolato, Luca; Demir, Kubilay; Balmer, Sophie; Bodak, Maxime; Boutros, Michael; Aaronson, Stuart; Mlodzik, Marek; Jenny, Andreas.

In: EMBO Reports, Vol. 14, No. 8, 08.2013, p. 718-725.

Research output: Contribution to journalArticle

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, vol. 14, no. 8, pp. 718-725. https://doi.org/10.1038/embor.2013.88
Serysheva E, Berhane H, Grumolato L, Demir K, Balmer S, Bodak M et al. Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. EMBO Reports. 2013 Aug;14(8):718-725. https://doi.org/10.1038/embor.2013.88
Serysheva, Ekatherina ; Berhane, Hebist ; Grumolato, Luca ; Demir, Kubilay ; Balmer, Sophie ; Bodak, Maxime ; Boutros, Michael ; Aaronson, Stuart ; Mlodzik, Marek ; Jenny, Andreas. / Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. In: EMBO Reports. 2013 ; Vol. 14, No. 8. pp. 718-725.
@article{b5c164b48faf4f0ab5d8afc2ceeae910,
title = "Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling",
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.",
keywords = "Dishevelled, Drosophila, Gordon syndrome, Wnk kinase, Wnt signalling",
author = "Ekatherina Serysheva and Hebist Berhane and Luca Grumolato and Kubilay Demir and Sophie Balmer and Maxime Bodak and Michael Boutros and Stuart Aaronson and Marek Mlodzik and Andreas Jenny",
year = "2013",
month = "8",
doi = "10.1038/embor.2013.88",
language = "English (US)",
volume = "14",
pages = "718--725",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling

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

PY - 2013/8

Y1 - 2013/8

N2 - 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.

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.

KW - Dishevelled

KW - Drosophila

KW - Gordon syndrome

KW - Wnk kinase

KW - Wnt signalling

UR - http://www.scopus.com/inward/record.url?scp=84881448107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881448107&partnerID=8YFLogxK

U2 - 10.1038/embor.2013.88

DO - 10.1038/embor.2013.88

M3 - Article

C2 - 23797875

AN - SCOPUS:84881448107

VL - 14

SP - 718

EP - 725

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 8

ER -