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- W4212950596 abstract "Aldosterone regulates volume homeostasis and blood pressure by enhancing sodium reabsorption in the kidney's distal nephron (DN). On the apical surface of these renal epithelia, aldosterone increases expression and activity of the thiazide-sensitive Na-Cl cotransporter (NCC) and the epithelial sodium channel (ENaC). While the cellular mechanisms by which aldosterone regulates ENaC have been well characterized, the molecular mechanisms that link aldosterone to NCC-mediated Na+/Cl- reabsorption remain elusive. The serine/threonine kinase with-no-lysine 4 (WNK4) has previously been shown to reduce cell surface expression of NCC. Here we measured sodium uptake in a Xenopus oocyte expression system and found that serum and glucocorticoid-induced kinase 1 (SGK1), an aldosterone-responsive gene expressed in the DN, attenuated the inhibitory effect of WNK4 on NCC activity. In addition, we showed--both in vitro and in a human kidney cell line--that SGK1 bound and phosphorylated WNK4. We found one serine located within an established SGK1 consensus target sequence, and the other within a motif that was, to our knowledge, previously uncharacterized. Mutation of these target serines to aspartate, in order to mimic phosphorylation, attenuated the effect of WNK4 on NCC activity in the Xenopus oocyte system. These data thus delineate what we believe to be a novel mechanism for aldosterone activation of NCC through SGK1 signaling of WNK4 kinase. PMID: 19690383 Funding information This work was supported by: PHS HHS, United States Grant ID: R01 051496 11 NIDDK NIH HHS, United States Grant ID: K08 DK 02723 NEI NIH HHS, United States Grant ID: 5P30EY010572 NCI NIH HHS, United States Grant ID: 5P30CA069533" @default.
- W4212950596 created "2022-02-24" @default.
- W4212950596 creator A5021081496 @default.
- W4212950596 creator A5048970112 @default.
- W4212950596 date "2009-09-11" @default.
- W4212950596 modified "2023-09-27" @default.
- W4212950596 title "Faculty Opinions recommendation of Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway." @default.
- W4212950596 doi "https://doi.org/10.3410/f.1163854.625676" @default.
- W4212950596 hasPublicationYear "2009" @default.
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