Signaling Pathways in Vasopressin-Mediated Regulation of Aquaporin-2

Vasopressin controls water excretion by regulating the water channel protein, aquaporin 2. Vasopressin acts in the renal collecting duct by binding to a G-protein coupled receptor and activating protein kinase A (PKA). Signaling events beyond PKA are largely unknown. Ultra-deep phosphoproteomic analysis of collecting duct cells isolated from rat kidneys identified and quantified 10,738 phosphorylation sites. Vasopressin significantly altered the abundance of only 219 of these phosphorylation sites, suggesting a highly selective effect on cell signaling. The regulated sites were mapped to cellular processes shown in prior studies to be involved in aquaporin-2 regulation. The mapping and full data set was used to create an online data resource to guide future studies.