Water excretion by the kidney is regulated by the neurohypophyseal peptide hormone vasopressin through actions in renal collecting duct cells to regulate the water channel protein aquaporin-2. Vasopressin signaling is initiated by binding to a G-protein–coupled receptor called V2R, which signals through heterotrimeric G-protein subunit Gsa, adenylyl cyclase 6, and activation of the cAMP-regulated protein kinase (PKA). Signaling events coupling PKA activation and aquaporin-2 regulation were largely unknown until the advent of modern protein mass spectrometry techniques that allow proteome-wide quantification of protein phosphorylation changes (phosphoproteomics). This short review documents phosphoproteomic findings in collecting duct cells describing the response to V2Rselective vasopressin agonists and antagonists, the response to CRISPR-mediated deletion of PKA, results from in vitro phosphorylation studies using recombinant PKA, the response to the broad-spectrum kinase inhibitor H89 (N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulphonamide), and the responses underlying lithium-induced nephrogenic diabetes insipidus. These phosphoproteomic data sets have been made available online for modeling vasopressin signaling and signaling downstream from other G-protein-coupled receptors.
CITATION STYLE
Salhadar, K., Matthews, A., Raghuram, V., Limbutara, K., Yang, C. R., Datta, A., … Knepper, M. A. (2021, May 1). Phosphoproteomic identification of vasopressin/cAMP/protein kinase A–dependent signaling in kidney. Molecular Pharmacology. American Society for Pharmacology and Experimental Therapy. https://doi.org/10.1124/MOL.120.119602
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