A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter

Chou Long Huang, Chih Jen Cheng

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2235-2241
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number11
DOIs
StatePublished - Apr 24 2015

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Sodium Chloride Symporters
Member 3 Solute Carrier Family 12
Phosphotransferases
Chlorides
Pseudohypoaldosteronism
Sodium-Potassium-Chloride Symporters
Hypertension
Mutation
Hyperkalemia
Protein-Serine-Threonine Kinases
Lysine
Perfusion
Chemical activation
Sensors

Keywords

  • Cullin3
  • Kelch-like
  • NCC
  • NKCC2
  • WNK1
  • WNK4

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter. / Huang, Chou Long; Cheng, Chih Jen.

In: Pflugers Archiv European Journal of Physiology, Vol. 467, No. 11, 24.04.2015, p. 2235-2241.

Research output: Contribution to journalArticle

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