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Wnk kinases are positive regulators of canonical Wnt/β‐catenin signalling
Author(s) -
Serysheva Ekatherina,
Berhane Hebist,
Grumolato Luca,
Demir Kubilay,
Balmer Sophie,
Bodak Maxime,
Boutros Michael,
Aaronson Stuart,
Mlodzik Marek,
Jenny Andreas
Publication year - 2013
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2013.88
Subject(s) - dishevelled , wnt signaling pathway , microbiology and biotechnology , kinase , biology , phosphorylation , lrp6 , signalling , frizzled , signal transduction
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.