Quantitative Phosphoproteomic Identification of Novel Vasopressin-mediated Signaling Networks in Kidney Distal Convoluted Tubule Cells

The kidney distal convoluted tubule (DCT) plays an important role in body sodium regulation and thus control of blood pressure. The main sodium reabsorption pathways in the DCT are the epithelial sodium channel (ENaC) and the thiazide-sensitive NaCl cotransporter (NCC), the functions of which can be modulated by the hormone vasopressin (VP) acting via uncharacterized signaling cascades. We performed large scale stable isotope labeling by amino acids in cell culture (SILAC) based quantitative phosphoproteomics of cultured mouse DCT cells (mpkDCT) to map global changes in protein phosphorylation events upon acute treatment with the VP type II receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP). The aim of this study is to identify unique VP signaling cascades in DCT cells that may be important for regulating ENaC or NCC activity. These pathways may be novel targets for modulation of blood pressure.