Document Detail


Molecular physiology of the WNK kinases.
MedLine Citation:
PMID:  17961084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in the serine-threonine kinases WNK1 and WNK4 cause a Mendelian disease featuring hypertension and hyperkalemia. In vitro and in vivo studies have revealed that these proteins are molecular switches that have discrete functional states that impart different effects on downstream ion channels, transporters, and the paracellular pathway. These effects enable the distal nephron to allow either maximal NaCl reabsorption or maximal K+ secretion in response to hypovolemia or hyperkalemia, respectively. The related kinase WNK3 has reciprocal actions on the primary mediators of cellular Cl(-) influx and efflux, effects that can serve to regulate cell volume during growth and in response to osmotic stress as well as to modulate neuronal responses to GABA. These findings define a versatile new family of kinases that coordinate the activities of diverse ion transport pathways to achieve and maintain fluid and electrolyte homeostasis.
Authors:
Kristopher T Kahle; Aaron M Ring; Richard P Lifton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annual review of physiology     Volume:  70     ISSN:  0066-4278     ISO Abbreviation:  Annu. Rev. Physiol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-02-14     Completed Date:  2008-05-16     Revised Date:  2012-06-26    
Medline Journal Info:
Nlm Unique ID:  0370600     Medline TA:  Annu Rev Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  329-55     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology*
Homeostasis / physiology
Humans
Intracellular Signaling Peptides and Proteins
Protein-Serine-Threonine Kinases / genetics*,  metabolism*
Water-Electrolyte Balance / physiology*
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; EC 2.7.1.-/Prkwnk4 protein, mouse; EC 2.7.11.1/Prkwnk1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/WNK1 protein, human; EC 2.7.11.1/WNK4 protein, human

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