SPAK Deficiency Corrects Pseudohypoaldosteronism II Caused by WNK4 Mutation
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منابع مشابه
SPAK Deficiency Corrects Pseudohypoaldosteronism II Caused by WNK4 Mutation
Stimulation of the OSR1 (Oxidative stress-responsive kinase-1)/SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase]-NCC (Na(+)-Cl(-) cotransporter) signaling cascade plays an important role in the WNK [With-No-Lysine (K)] kinase 4 D561A knock-in mouse model of pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. The aim of this st...
متن کاملPhenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade.
We recently reported increased phosphorylation of the NaCl cotransporter (NCC) in Wnk4(D561A/+) knock-in mice, an ideal model of the human hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Although previous in vitro studies had suggested the existence of a phosphorylation cascade involving the WNK, OSR1 and SPAK kinases, whether the WNK-OSR1/SPAK cascade is in fact fully ...
متن کاملWNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4.
The epithelial Ca(2+) channel TRPV5 serves as a gatekeeper for active Ca(2+) reabsorption in the distal convoluted tubule and connecting tubule of the kidney. WNK4, a protein serine/threonine kinase with gene mutations that cause familial hyperkalemic hypertension (FHH), including a subtype with hypercalciuria, is also localized in the distal tubule of the nephron. To understand the role of WNK...
متن کاملWNK4 is the major WNK positively regulating NCC in the mouse kidney
By analysing the pathogenesis of a hereditary hypertensive disease, PHAII (pseudohypoaldosteronism type II), we previously discovered that WNK (with-no-lysine kinase)-OSR1/SPAK (oxidative stress-responsive 1/Ste20-like proline/alanine-rich kinase) cascade regulates NCC (Na-Cl co-transporter) in the DCT (distal convoluted tubules) of the kidney. However, the role of WNK4 in the regulation of NCC...
متن کاملCharacterization of the kinase activity of a WNK4 protein complex.
Mutations in WNK4 protein kinase cause pseudohypoaldosteronism type II (PHAII), a genetic disorder that is characterized by renal NaCl and K(+) retention leading to hypertension and hyperkalemia. Consistent with this, WNK4 is known to regulate several renal tubule transporters, including the NaCl cotransporter, NCC, and the K(+) channel, ROMK, but the mechanisms are incompletely understood, and...
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ژورنال
عنوان ژورنال: PLoS ONE
سال: 2013
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0072969