Phosphoproteomic Identification of Vasopressin V2 Receptor-Dependent Signaling in the Renal Collecting Duct.

Phosphoproteomic Identification of Vasopressin V2 Receptor-Dependent Signaling in the Renal Collecting Duct.
Am J Physiol Renal Physiol. 2019 Jul 17;:
Authors: Deshpande V, Kao AR, Raghuram V, Datta A, Chou CL, Knepper MA
Abstract
Vasopressin controls water balance largely through protein kinase A (PKA)-dependent effects to regulate the collecting-duct water channel aquaporin-2 (AQP2). Although considerable information has accrued regarding regulation of water and solute transport in collecting duct cells, information is sparse regarding the signaling connections between PKA and transport responses. Here, we exploit recent advancements in protein mass spectrometry to carry out a comprehensive, multiple-replicate analysis of changes in the phosphoproteome of native rat inner medullary collecting duct cells in response to the V2-selective vasopressin analog dDAVP. Of 10,738 phosphopeptides quantified, only 156 were significantly increased in abundance and only 63 were decreased, indicative of a highly selective response to vasopressin. The list of upregulated phospho-sites showed several general characteristics: (a) a preponderance of sites having a basic motif (R/K-R/K-X-p[S/T]) consistent with phosphorylation by PKA and/or other basophilic kinases; (b) a greater-than-random likelihood of sites previously demonstrated to be phosphorylated by PKA; (c) a preponderance of sites in membrane proteins, consistent with regulation by membrane...

Source: American Journal of Physiology. Renal Physiology - July 16, 2019 Category: Physiology Authors: Deshpande V, Kao AR, Raghuram V, Datta A, Chou CL, Knepper MA Tags: Am J Physiol Renal Physiol Source Type: research