The WNK kinase network regulating sodium, potassium, and blood pressure

Ewout J. Hoorn, Joshua H. Nelson, James (Jim) McCormick, David Ellison

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The relationship between renal salt handling and hypertension is intertwined historically. The discovery of WNK kinases (With No lysine = K) now offers new insight to this relationship because WNKs are a crucial molecular pathway connecting hormones such as angiotensin II and aldosterone to renal sodium and potassium transport. To fulfill this task, the WNKs also interact with other important kinases, including serum and glucocorticoid-regulated kinase 1, STE20/SPS1-related, proline alanine-rich kinase, and oxidative stress responsive protein type 1. Collectively, this kinase network regulates the activity of the major sodium and potassium transporters in the distal nephron, including thiazide-sensitive Na-Cl cotransporters and ROMK channels. Here we show how the WNKs modulate ion transport through two distinct regulatory pathways, trafficking and phosphorylation, and discuss the physiologic and clinical relevance of the WNKs in the kidney. This ranges from rare mutations in WNKs causing familial hyperkalemic hypertension to acquired forms of hypertension caused by salt sensitivity or diabetes mellitus. Although many questions remain unanswered, the WNKs hold promise for unraveling the link between salt and hypertension, potentially leading to more effective interventions to prevent cardiorenal damage.

Original languageEnglish (US)
Pages (from-to)605-614
Number of pages10
JournalJournal of the American Society of Nephrology
Volume22
Issue number4
DOIs
StatePublished - Apr 2011

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Potassium
Phosphotransferases
Sodium
Blood Pressure
Hypertension
Salts
Kidney
Nephrons
Ion Transport
Heat-Shock Proteins
Aldosterone
Proline
Angiotensin II
Alanine
Lysine
Diabetes Mellitus
Oxidative Stress
Phosphorylation
Hormones
Mutation

ASJC Scopus subject areas

  • Nephrology

Cite this

The WNK kinase network regulating sodium, potassium, and blood pressure. / Hoorn, Ewout J.; Nelson, Joshua H.; McCormick, James (Jim); Ellison, David.

In: Journal of the American Society of Nephrology, Vol. 22, No. 4, 04.2011, p. 605-614.

Research output: Contribution to journalArticle

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