Arginine vasopressin regulates the renal Na+-Cl– and Na+-K+-Cl– cotransporters through with-no-lysine kinase 4 and inhibitor 1 phosphorylation

With-no-lysine kinases regulate the phosphorylation and activity of the Na + -Cl – and Na + -K + -2Cl – cotransporters. This pathway is modulated by arginine vasopressin (AVP). However, the link between AVP and WNK signaling remains unknown. Here, we show that AVP activates WNK4 through increased phosphorylation at putative protein kinase A-regulated sites and decreases its dephosphorylation by protein phosphatase 1. This work increases our understanding of the signaling pathways mediating AVP actions in the kidney.