Mutations in the serine-threonine kinases WNK1 and WNK4 cause a Mendelian disease featuring hypertension and hyperkalemia. In vitro and in vivo studies have revealed that these proteins are molecular switches that have discrete functional states that impart different effects on downstream ion channels, transporters, and the paracellular pathway. These effects enable the distal nephron to allow either maximal NaCl reabsorption or maximal K+ secretion in response to hypovolemia or hyperkalemia, respectively. The related kinase WNK3 has reciprocal actions on the primary mediators of cellular Cl(-) influx and efflux, effects that can serve to regulate cell volume during growth and in response to osmotic stress as well as to modulate neuronal responses to GABA. These findings define a versatile new family of kinases that coordinate the activities of diverse ion transport pathways to achieve and maintain fluid and electrolyte homeostasis.

中文翻译：

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WNK激酶的分子生理学。

丝氨酸-苏氨酸激酶WNK1和WNK4的突变会导致孟德尔疾病，高血压和高钾血症。体外和体内研究表明，这些蛋白质是具有离散功能状态的分子开关，这些功能状态对下游离子通道，转运蛋白和旁细胞途径具有不同的作用。这些作用使远端肾单位分别响应血容量不足或高钾血症而允许最大的NaCl重吸收或最大的K +分泌。相关的激酶WNK3对细胞C1（-）流入和流出的主要介体具有交互作用，这种作用可在生长过程中调节细胞体积并响应渗透压以及调节神经元对GABA的响应。