期刊
EMBO REPORTS
卷 14, 期 8, 页码 718-725出版社
WILEY
DOI: 10.1038/embor.2013.88
关键词
Dishevelled; Drosophila; Gordon syndrome; Wnk kinase; Wnt signalling
资金
- American Heart Association [13GRNT14680002]
- National Institute of Health [GM088202, EY13256, HD66319]
- INSERM
- University of Rouen
- Deutsche Forschungsgemeinschaft
- European Commission ('MC-EXT Cellular Signaling')
- European Commission ('CancerPathways')
Wnt/beta-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/b-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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