Extrarenal roles of the with‐no‐lysine[K] kinases (WNKs). (December 2013)

• Record Type: Journal Article
• Authors: Siew, Keith; O'Shaughnessy, Kevin M
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 40:Number 12(2013:Dec.)
• Page Start: 885
• Page End: 894
• Publication Date: 2013-12
• Subjects: Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.12108
• Languages: English
• ISSNs: 0305-1870

Abstract

<abstract abstract-type="main" id="cep12108-abs-0001"> <title>Summary</title> <p> <list id="cep12108-list-0001" list-type="order"> <list-item> <p>Identified over a decade ago, the with‐no‐lysine[K] kinases (WNKs) have been the subsequent focus of intense research into the renal handling of Na<sup>+</sup>, Cl<sup>−</sup> and K<sup>+</sup> and several rare monogenetic diseases. However, the potential extrarenal roles for WNKs have been less well explored.</p> </list-item> <list-item> <p>Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca<sup>2+</sup> and PO<sub>4</sub><sup>3−</sup> homeostasis, which were originally assumed to be an indirect effect through the kidney. However, current data suggest a complex and direct role for WNKs in the physiology of bone.</p> </list-item> <list-item> <p>The WNKs also modulate systemic blood pressure at several levels, including the vascular resistance vessels, where they cause vasoconstriction by altering the abundance of the transient receptor potential canonical channel 3 and/or phosphorylation of the Na<sup>+</sup>−K<sup>+</sup>−2Cl<sup>−</sup> cotransporter 1 in vascular smooth muscle cells.</p> </list-item> <list-item> <p>The WNKs and many of the cation‐coupled Cl<sup>−</sup> cotransporters they regulate are highly expressed in the central nervous system and recent work suggests that WNK dysfunction may have a role in the development of autism, schizophrenia and hereditary sensory and autonomic neuropathy Type 2.</p> </list-item> <list-item> <p>Finally, the WNK–sterile 20 kinase signalling axis represents an evolutionarily ancient mechanism for maintaining osmotic homeostasis, but a rapidly expanding body of evidence also shows a role in immunity and cellular regulation.</p> </list-item> </list> </p> </abstract>