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Annual Review of Physiology

Volume 85, 2023

Intracellular Ion Control of WNK Signaling

Abstract

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.

Keyword(s): inflammasome, ion transport, KCC, Malpighian tubule, NKCC, SPAK
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/content/journals/10.1146/annurev-physiol-031522-080651
2023-02-10
2025-04-18
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/content/journals/10.1146/annurev-physiol-031522-080651
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Intracellular Ion Control of WNK Signaling
Annual Review of Physiology 85, 383 (2023); https://doi.org/10.1146/annurev-physiol-031522-080651
/content/journals/10.1146/annurev-physiol-031522-080651
/content/journals/10.1146/annurev-physiol-031522-080651
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