Journal article
A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter
Pflügers Archiv, Vol.467(11), pp.2235-2241
11/2015
DOI: 10.1007/s00424-015-1708-2
PMCID: PMC4601926
PMID: 25904388
Abstract
Mammalian with-no-lysine [K] (WNK) kinases are a family of four serine-threonine protein kinases, WNK1-4. Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. Increased Na(+) reabsorption through Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule plays an important role in the pathogenesis of hypertension in patients with PHA2. However, how WNK1 and WNK4 regulate NCC and how mutations of WNKs cause activation of NCC have been controversial. Here, we review current state of literature supporting a compelling model that WNK1 and WNK4 both contribute to stimulation of NCC. The precise combined effects of WNK1 and WNK4 on NCC remain unclear but likely are positive rather than antagonistic. The recent discovery that WNK kinases may function as an intracellular chloride sensor adds a new dimension to the physiological role of WNK kinases. Intracellular chloride-dependent regulation of WNK's may underlie the mechanism of regulation of NCC by extracellular K(+). Definite answer yet will require future investigation by tubular perfusion in mice with altered WNK kinase expression.
Details
- Title: Subtitle
- A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter
- Creators
- Chou-Long Huang - Department of Internal Medicine, Division of Nephrology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-8856, USA. Chou-Long.Huang@UTSouthwestern.eduChih-Jen Cheng - Department of Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Resource Type
- Journal article
- Publication Details
- Pflügers Archiv, Vol.467(11), pp.2235-2241
- DOI
- 10.1007/s00424-015-1708-2
- PMID
- 25904388
- PMCID
- PMC4601926
- NLM abbreviation
- Pflugers Arch
- ISSN
- 0031-6768
- eISSN
- 1432-2013
- Grant note
- R01 DK059530 / NIDDK NIH HHS DK59530 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/2015
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094503302771
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