Wnk kinase in Wnt signaling and development
Wnt/Wingless (Wg) growth factors commonly signal through either the canonical Wnt (Wg)/β-catenin pathway or through non-canonical Wnt pathways such as the Wnt/Fz-planar cellular polarity (PCP) pathway, regulating the polarization of cells within the pane of the epithelium. These two pathways are highly conserved between humans, mice, fish and flies.
Canonical Wnt/β-catenin signaling is essential for many aspects of development. For example in vertebrates, it controls the specification of the dorsal-ventral (D-V) embryonic axis, cell proliferation in many tissues, maintenance of stem cells, and vascularization. Aberrant canonical Wnt signaling in humans causes cancer.
Using phosphorylation of the Wnt adapter Dishevelled as a readout, we identified Wnk (With No Lysine [K]) kinase as a conserved, novel regulator of peak canonical Wnt signaling. WNK kinases are well known for their role in the regulation of ion homeostasis in the kidney, where autosomal dominant mutations cause Gordon’s syndrome (a.k.a. Pseudohypoaldosteronism Type II) characterized by hypertension and hyperkalemia.
We are assessing the mechanism of Wnt dependent and independent functions of Wnk during fly development. Our studies will advance our understanding of Wnk-dependent organogenesis and have relevance for important clinical areas including cardiovascular development and cancer.
