WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis

Significance Deletion of WNK1 in mice causes embryonic lethality due to failed vascular development. WNK1 is best known for its importance in blood pressure control; mutations in the gene can lead to Gordon’s syndrome. Much of WNK1 signaling is mediated by downstream protein kinases OSR1 (oxidative stress responsive 1) and SPAK (STE20/SPS1-related proline-, alanine-rich kinase). This study characterizes an essential contribution of WNK1 in angiogenesis by influencing processes regulated by transforming growth factor-β (TGF-β) and presents a mechanism of tight junction and adherens junction turnover through interaction with OSR1. Collaborations between WNK1/OSR1 and TGF-β mediators are identified that fine tune essential processes in angiogenesis and may contribute to context-specificity in TGF-β signaling, with implications in development, wound repair, and cancer biology.

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