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

E Serysheva, H Berhane, L Grumolato, K Demir… - EMBO …, 2013 - embopress.org
E Serysheva, H Berhane, L Grumolato, K Demir, S Balmer, M Bodak, M Boutros, S Aaronson…
EMBO reports, 2013embopress.org
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 …
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.
embopress.org