WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron

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57 Citations (Scopus)

Abstract

With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K+ secretion.

Original languageEnglish (US)
Pages (from-to)630-634
Number of pages5
JournalKidney International
Volume70
Issue number4
DOIs
StatePublished - Aug 28 2006

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Thiazides
Nephrons
Aldosterone
Sodium Chloride
Potassium
Phosphotransferases
Epithelial Sodium Channels
Symporters
Kidney
Hyperkalemia
Protein-Serine-Threonine Kinases
Potassium Channels
Protein Transport
Genes
Lysine
Chlorides
Catalytic Domain
Ions
Hypertension
Mutation

Keywords

  • Distal convoluted tubule
  • ENaC
  • NCC
  • ROMK
  • WNK

ASJC Scopus subject areas

  • Nephrology

Cite this

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abstract = "With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K+ secretion.",
keywords = "Distal convoluted tubule, ENaC, NCC, ROMK, WNK",
author = "Subramanya, {A. R.} and Chao-Ling Yang and McCormick, {James (Jim)} and David Ellison",
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T1 - WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron

AU - Subramanya, A. R.

AU - Yang, Chao-Ling

AU - McCormick, James (Jim)

AU - Ellison, David

PY - 2006/8/28

Y1 - 2006/8/28

N2 - With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K+ secretion.

AB - With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K+ secretion.

KW - Distal convoluted tubule

KW - ENaC

KW - NCC

KW - ROMK

KW - WNK

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JO - Kidney International

JF - Kidney International

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