Journal Article

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

Demir, Kubilay, Bodak, Maxime, Aaronson, Stuart, Balmer, Sophie, Grumolato, Luca, Mlodzik, Marek, Berhane, Hebist, Serysheva, Ekatherina, Jenny, Andreas, Boutros, Michael

2013

Overview

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. This study identifies a novel role for Wnk kinases in canonical Wnt signalling that appears to be conserved from Drosophila to humans.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,EMBO Press,Nature Publishing Group
• Subject: Adaptor Proteins, Signal Transducing / Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - metabolism / Animals / beta Catenin / beta Catenin - genetics / beta Catenin - metabolism / Dishevelled / Dishevelled Proteins / Drosophila / Drosophila melanogaster / Drosophila Proteins / EMBO11 / Gene Expression Regulation / Gordon syndrome / HEK293 Cells / Humans / Intracellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins - antagonists & inhibitors / Intracellular Signaling Peptides and Proteins - genetics / Intracellular Signaling Peptides and Proteins - metabolism / Lentivirus / Lentivirus - genetics / Life Sciences / Minor Histocompatibility Antigens / Phosphoproteins / Phosphoproteins - genetics / Phosphoproteins - metabolism / Phosphorylation / Protein Serine-Threonine Kinases / Protein-Serine-Threonine Kinases - antagonists & inhibitors / Protein-Serine-Threonine Kinases - genetics / Protein-Serine-Threonine Kinases - metabolism / RNA, Small Interfering / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Scientific Report / Scientific Reports / Wnk kinase / WNK Lysine-Deficient Protein Kinase 1 / Wnt Signaling Pathway / Wnt Signaling Pathway - genetics / Wnt signalling