The WNKs

Atypical protein kinases with pleiotropic actions

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

WNKs are serine/threonine kinases that comprise a unique branch of the kinome. They are so-named owing to the unusual placement of an essential catalytic lysine. WNKs have now been identified in diverse organisms. In humans and other mammals, four genes encode WNKs. WNKs are widely expressed at the message level, although data on protein expression is more limited. Soon after the WNKs were identified, mutations in genes encoding WNK1 and -4 were determined to cause the human disease familial hyperkalemic hypertension (also known as pseudohypoaldosteronism II, or Gordon's Syndrome). For this reason, a major focus of investigation has been to dissect the role of WNK kinases in renal regulation of ion transport. More recently, a different mutation in WNK1 was identified as the cause of hereditary sensory and autonomic neuropathy type II, an early-onset autosomal disease of peripheral sensory nerves. Thus the WNKs represent an important family of potential targets for the treatment of human disease, and further elucidation of their physiological actions outside of the kidney and brain is necessary. In this review, we describe the gene structure and mechanisms regulating expression and activity of the WNKs. Subsequently, we outline substrates and targets of WNKs as well as effects of WNKs on cellular physiology, both in the kidney and elsewhere. Next, consequences of these effects on integrated physiological function are outlined. Finally, we discuss the known and putative pathophysiological relevance of the WNKs.

Original languageEnglish (US)
Pages (from-to)177-219
Number of pages43
JournalPhysiological Reviews
Volume91
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Protein Kinases
Kidney
Pseudohypoaldosteronism
Hereditary Sensory and Autonomic Neuropathies
Genes
Mutation
Protein-Serine-Threonine Kinases
Ion Transport
Peripheral Nervous System Diseases
Lysine
Mammals
Phosphotransferases
Hypertension
Brain
Proteins
Gordon syndrome

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

Cite this

The WNKs : Atypical protein kinases with pleiotropic actions. / McCormick, James (Jim); Ellison, David.

In: Physiological Reviews, Vol. 91, No. 1, 01.2011, p. 177-219.

Research output: Contribution to journalArticle

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