PMID:23797875

Citation	Serysheva, E, Berhane, H, Grumolato, L, Demir, K, Balmer, S, Bodak, M, Boutros, M, Aaronson, S, Mlodzik, M and Jenny, A (2013) Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. EMBO Rep. 14:718-25
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.
Links	PubMed PMC3736130 Online version:10.1038/embor.2013.88
Keywords	Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Dishevelled Proteins; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Lentivirus/genetics; Minor Histocompatibility Antigens; Phosphoproteins/genetics; Phosphoproteins/metabolism; Phosphorylation; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; WNK Lysine-Deficient Protein Kinase 1; Wnt Signaling Pathway/genetics; beta Catenin/genetics; beta Catenin/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DROME:M9PGC5	enables	GO:0004672: protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(FB:FBgn0023083)	Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0046777: protein autophosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0006468: protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0090263: positive regulation of canonical Wnt signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0090263: positive regulation of canonical Wnt signaling pathway	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0000499	P		Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0090263: positive regulation of canonical Wnt signaling pathway	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0016797	P		Seeded From UniProt	complete
DROME:M9PGC5	involved_in	GO:0035220: wing disc development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q7KSD3	involved_in	GO:0035220: wing disc development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WNK1	involved_in	GO:0090263: positive regulation of canonical Wnt signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WNK2	involved_in	GO:0090263: positive regulation of canonical Wnt signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WNT3A	involved_in	GO:0060070: canonical Wnt signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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