We identified the protein kinase WNK1 (With No lysine (K) 1) by low stringency cloning, determined the structure of its uniquely organized catalytic domain, demonstrated its sensitivity to osmotic state, and identified regulation of primary downstream protein kinases and ion transporters.  To date, ion transport has been the WNK1 focal point because mutations that increase its expression in kidney cause a rare form of hypertension.  Whole-body and endothelial-selective disruption of the mouse WNK1 gene by Chou-Long Huang (Internal Medicine, UTSW) produce the same phenotype: death at E11-12 due to failed remodeling of the embryonic vasculature.  These results reveal an absolute developmental requirement for WNK1 in the endothelium.  By scrutinizing endothelial cells in two- and three-dimensional assays, we found that WNK1 is required for migration, directional movement, forming oriented cell-cell contacts, and sprouting from a formed endothelial cord or tube.  At a molecular level, WNK1 is required for expression of the mesenchymal transcription factor Slug (SNAI2) and for small GTPase-mediated actin dynamics, to initiate cell movement from an otherwise differentiated tissue.  We have also determined other WNK1-regulated events that are important for its unique biological actions. We are studying WNK1 signaling mechanisms crucial for vessel restructuring and repair, its actions on vesicular trafficking and cell migration, and the importance of WNK1 in cancer.