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Reciprocal regulation of aquaporin-2 abundance and degradation by protein kinase A and p38-MAP kinase

Item Type:Article
Title:Reciprocal regulation of aquaporin-2 abundance and degradation by protein kinase A and p38-MAP kinase
Creators Name:Nedvetsky, P.I., Tabor, V., Tamma, G., Beulshausen, S., Skroblin, P., Kirschner, A., Mutig, K., Boltzen, M., Petrucci, O., Vossenkaemper, A., Wiesner, B., Bachmann, S., Rosenthal, W. and Klussmann, E.
Abstract:Arginine-vasopressin (AVP) modulates the water channel aquaporin-2 (AQP2) in the renal collecting duct to maintain homeostasis of body water. AVP binds to vasopressin V2 receptors (V2R), increasing cAMP, which promotes the redistribution of AQP2 from intracellular vesicles into the plasma membrane. cAMP also increases AQP2 transcription, but whether altered degradation also modulates AQP2 protein levels is not well understood. Here, elevation of cAMP increased AQP2 protein levels within 30 minutes in primary inner medullary collecting duct (IMCD) cells, in human embryonic kidney (HEK) 293 cells ectopically expressing AQP2, and in mouse kidneys. Accelerated transcription or translation did not explain this increase in AQP2 abundance. In IMCD cells, cAMP inhibited p38-mitogen-activated protein kinase (p38-MAPK) via activation of protein kinase A (PKA). Inhibition of p38-MAPK associated with decreased phosphorylation (serine 261) and polyubiquitination of AQP2, preventing proteasomal degradation. Our results demonstrate that AVP enhances AQP2 protein abundance by altering its proteasomal degradation through a PKA- and p38-MAPK-dependent pathway.
Keywords:Aquaporin 2, Arginine Vasopressin, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Forskolin, Kidney Medulla, Collecting Kidney Tubules, Phosphorylation, Proteasome Endopeptidase Complex, Protein Biosynthesis, Genetic Transcription, p38 Mitogen-Activated Protein Kinases, Animals, Mice, Rats
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:1645-1656
Date:October 2010
Official Publication:https://doi.org/10.1681/ASN.2009111190
PubMed:View item in PubMed

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