JCI - Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway

Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway

David J. Rozansky, Tonya Cornwall, Arohan R. Subramanya, Shaunessy Rogers, Yong-Feng Yang, Larry L. David, Xiaoman Zhu, Chao-Ling Yang, David H. Ellison

Published in Volume 119, Issue 9

J Clin Invest. 2009; 119(9):2601–2612 doi:10.1172/JCI38323

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Figure 1

The active form of SGK1 reverses WNK4 inhibition of NCC-mediated Na⁺ uptake in Xenopus oocytes.

(A) Schematic diagram of the DCT, outlining the hypothesis of where SGK1 acts to influence WNK4 inhibition of Na⁺/Cl^– cotransport (shown by thick arrows). The question mark and dashed line indicate the area of interest for this study. Arrows denote SGK1 movement among inactive, active, and degraded forms. Stimulatory and inhibitory effects are indicated by filled circles and blunt-headed arrows, respectively. Phosphorylation steps are denoted by “P.” (B) Representative sample of formaldehyde/agarose gel stained with ethidium bromide showing equivalent amounts of SGK/S422D and SGK/K127M cRNA and no obvious degradation prior to injection into oocytes. Lanes were run on the same gel, which was split to maintain the sample order in C. (C) Relative to NCC alone, WNK4 reduced NCC-mediated Na⁺ flux by 60%. The addition of constitutively active SGK1/S422D reversed that effect, whereas addition of kinase-dead SGK1/K127M continued to reduce Na⁺ flux. n = 3 for each condition (± SEM). Significance (by ANOVA) is indicated.