title: Molecular physiology of the WNK kinases.
abstract: 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.affiliation: Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Kahle
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Ring
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; C499024:Prkwnk4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; C433806:WNK4 protein, human; C498744:Wnk1 protein, mouse