Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2005-12-26
pubmed:abstractText
The WNK1 and WNK4 genes have been found to be mutated in some patients with hyperkalemia and hypertension caused by pseudohypoaldosteronism type II. The clue to the pathophysiology of pseudohypoaldosteronism type II was its striking therapeutic response to thiazide diuretics, which are known to block the sodium chloride cotransporter (NCC). Although this suggests a role for WNK1 in hypertension, the precise molecular mechanisms are largely unknown. Here we have shown that WNK1 phosphorylates and regulates the STE20-related kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). WNK1 was observed to phosphorylate the evolutionary conserved serine residue located outside the kinase domains of SPAK and OSR1, and mutation of the OSR1 serine residue caused enhanced OSR1 kinase activity. In addition, hypotonic stress was shown to activate SPAK and OSR1 and induce phosphorylation of the conserved OSR1 serine residue, suggesting that WNK1 may be an activator of the SPAK and OSR1 kinases. Moreover, SPAK and OSR1 were found to directly phosphorylate the N-terminal regulatory regions of cation-chloride-coupled cotransporters including NKCC1, NKCC2, and NCC. Phosphorylation of NCC was induced by hypotonic stress in cells. These results suggested that WNK1 and SPAK/OSR1 mediate the hypotonic stress signaling pathway to the transporters and may provide insights into the mechanisms by which WNK1 regulates ion balance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cations, http://linkedlifedata.com/resource/pubmed/chemical/Chlorides, http://linkedlifedata.com/resource/pubmed/chemical/Diuretics, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Ions, http://linkedlifedata.com/resource/pubmed/chemical/JIK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/OXSR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Osr1 kinase, rat, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/STK39 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Serine, http://linkedlifedata.com/resource/pubmed/chemical/WNK1 protein, human
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42685-93
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16263722-Amino Acid Motifs, pubmed-meshheading:16263722-Amino Acid Sequence, pubmed-meshheading:16263722-Animals, pubmed-meshheading:16263722-Biological Transport, pubmed-meshheading:16263722-Cations, pubmed-meshheading:16263722-Cell Line, pubmed-meshheading:16263722-Chlorides, pubmed-meshheading:16263722-Cloning, Molecular, pubmed-meshheading:16263722-Conserved Sequence, pubmed-meshheading:16263722-Diuretics, pubmed-meshheading:16263722-Dogs, pubmed-meshheading:16263722-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16263722-Enzyme Activation, pubmed-meshheading:16263722-Escherichia coli, pubmed-meshheading:16263722-Evolution, Molecular, pubmed-meshheading:16263722-Glutathione Transferase, pubmed-meshheading:16263722-Humans, pubmed-meshheading:16263722-Hypertension, pubmed-meshheading:16263722-Immunoblotting, pubmed-meshheading:16263722-Immunoprecipitation, pubmed-meshheading:16263722-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16263722-Ions, pubmed-meshheading:16263722-Mass Spectrometry, pubmed-meshheading:16263722-Mice, pubmed-meshheading:16263722-Molecular Sequence Data, pubmed-meshheading:16263722-Nerve Tissue Proteins, pubmed-meshheading:16263722-Phosphorylation, pubmed-meshheading:16263722-Protein Kinases, pubmed-meshheading:16263722-Protein Structure, Tertiary, pubmed-meshheading:16263722-Protein-Serine-Threonine Kinases, pubmed-meshheading:16263722-Rats, pubmed-meshheading:16263722-Recombinant Fusion Proteins, pubmed-meshheading:16263722-Sequence Homology, Amino Acid, pubmed-meshheading:16263722-Serine, pubmed-meshheading:16263722-Signal Transduction, pubmed-meshheading:16263722-Two-Hybrid System Techniques
pubmed:year
2005
pubmed:articleTitle
WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.
pubmed:affiliation
Department of Molecular Cell Biology, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, and CREST, JST, Chiyoda, Tokyo 101-0062.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't