title: Regulation of Renal Electrolyte Transport by WNK and SPAK-OSR1 Kinases.
abstract: The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. WNKs regulate the activity of the Na(+):Cl(-) cotransporter (NCC), the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), and other transport pathways. Interestingly, the modulation of NCC occurs via the phosphorylation by WNKs of other serine-threonine kinases known as SPAK-OSR1. In contrast, the process of regulating the channels is independent of SPAK-OSR1. We present a review of the remarkable advances in this area in the past 10 years.
authors: INSERM UMR970, Paris Cardiovascular Research Center, 75015 Paris, France.|Faculty of Medicine, Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France.
authors: Juliette
authors: J
authors: Hadchouel
authors: Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon 97239.
authors: David H
authors: DH
authors: Ellison
authors: Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City 14080, Mexico; email: gamba@biomedicas.unam.mx.
authors: Gerardo
authors: G
authors: Gamba
mesh_terms: D000818:Animals; D004573:Electrolytes / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology*; D007668:Kidney / Q000378:metabolism* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011546:Pseudohypoaldosteronism / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004573:Electrolytes; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases
keywords: ENaC; NCC; ROMK; SLC12; diuretics; hypertension; salt transport