| http://purl.uniprot.org/citations/24039833 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24039833 | http://www.w3.org/2000/01/rdf-schema#comment | "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 study was to investigate the respective roles of Osr1 and Spak in the pathogenesis of PHA II in vivo. Wnk4 (D561A/+) mice were crossed with kidney tubule-specific (KSP) Osr1 knockout (KSP-Osr1 (-/-)) and Spak knockout (Spak (-/-)) mice. Blood pressure, plasma and urine biochemistries, and the relevant protein expression in the kidneys were examined. Wnk4 (D561A/+), KSP-Osr1 (-/-), and Spak (-/-) mice recapitulated the phenotypes of PHA II, Bartter-like syndrome, and Gitelman syndrome, respectively. Wnk4 (D561A/+).KSP-Osr1 (-/-) remained phenotypically PHA II while Wnk4 (D561A/+).Spak (-/-) mice became normotensive and lacked the PHA II phenotype. Phosphorylated Spak and Ncc were similarly increased in both Wnk4 (D561A/+) and Wnk4 (D561A/+).KSP-Osr1 (-/-) mice while phosphorylated Ncc normalized in Wnk4 (D561A/+).Spak (-/-) mice. Furthermore, Wnk4 (D561A/+).KSP-Osr1 (-/-) mice exhibited exaggerated salt excretion in response to thiazide diuretics while Wnk4 (D561A/+).Spak (-/-) mice exhibited normal responses. Wnk4(D561A/+).Spak (-/-).KSP-Osr1 (-/-) triple mutant mice had low blood pressure and diminished phosphorylated Ncc. Both SPAK and OSR1 are important in the maintenance of blood pressure but activation of SPAK-NCC plays the dominant role in PHA II. SPAK may be a therapeutic target for disorders with salt-sensitive hypertension related to WNK4 activation."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0072969"xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Wu Y.C."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Sasaki S."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Uchida S."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Yang S.S."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Lin S.H."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Fang Y.W."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Chu P.Y."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Cheng C.J."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/author | "Chau T."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/pages | "e72969"xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/title | "SPAK deficiency corrects pseudohypoaldosteronism II caused by WNK4 mutation."xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/24039833 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24039833 |
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