title: A novel protein kinase signaling pathway essential for blood pressure regulation in humans.
abstract: The discovery that mutations in WNK4 [encoding a member of the WNK family - so named because of the unique substitution of cysteine for lysine at a nearly invariant residue within subdomain II of its catalytic core: with no K (lysine)] cause pseudohypoaldosteronism type II, an autosomal dominant form of human hypertension, provided the initial clue that this serine/threonine kinase is a crucial part of a complex renal salt regulatory system. Recent findings from physiological studies of WNK4 in Xenopus laevis oocytes, mammalian cell systems and in vivo in mouse models have provided novel insights into the mechanisms by which the kidney regulates salt homeostasis, and therefore blood pressure, downstream of aldosterone signaling in mammals. The current evidence supports a model in which WNK4 coordinates the activities of diverse aldosterone-sensitive mediators of ion transport in the distal nephron to promote normal homeostasis in response to physiological perturbation.
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. kkahle@partners.org
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Kahle
authors.forename: Jesse
authors.initials: J
authors.lastname: Rinehart
authors.forename: Gerhard
authors.initials: G
authors.lastname: Giebisch
authors.forename: Gerardo
authors.initials: G
authors.lastname: Gamba
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hebert
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D029867:Xenopus Proteins; C499024:Prkwnk4 protein, mouse; D017346:Protein Serine-Threonine Kinases; C519693:WNK4 protein, Xenopus; C433806:WNK4 protein, human