Intracellular Ion Control of WNK Signaling

Research output: Contribution to journalReview articlepeer-review


The with no lysine (K) (WNK) kinases are an evolutionarily ancient group of kinases with atypical placement of the catalytic lysine and diverse physiological roles. Recent studies have shown that WNKs are directly regulated by chloride, potassium, and osmotic pressure. Here, we review the discovery of WNKs as chloride-sensitive kinases and discuss physiological contexts in which chloride regulation of WNKs has been demonstrated. These include the kidney, pancreatic duct, neurons, and inflammatory cells. We discuss the interdependent relationship of osmotic pressure and intracellular chloride in cell volume regulation. We review the recent demonstration of potassium regulation of WNKs and speculate on possible physiological roles. Finally, structural and mechanistic aspects of intracellular ion and osmotic pressure regulation of WNKs are discussed.

Original languageEnglish (US)
Pages (from-to)383-406
Number of pages24
JournalAnnual review of physiology
StatePublished - Feb 10 2023


  • inflammasome
  • ion transport
  • KCC
  • Malpighian tubule
  • NKCC
  • SPAK

ASJC Scopus subject areas

  • Physiology


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