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Extrarenal roles of the with‐no‐lysine[ K ] kinases ( WNK s)
Author(s) -
Siew Keith,
O'Shaughnessy Kevin M
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12108
Subject(s) - kinase , homeostasis , cotransporter , distal convoluted tubule , microbiology and biotechnology , phosphorylation , chemistry , endocrinology , biology , medicine , kidney , reabsorption , sodium , organic chemistry
Summary Identified over a decade ago, the with‐no‐lysine[K] kinases ( WNK s) have been the subsequent focus of intense research into the renal handling of Na + , Cl − and K + and several rare monogenetic diseases. However, the potential extrarenal roles for WNK s have been less well explored. Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca 2+ and PO 4 3− homeostasis, which were originally assumed to be an indirect effect through the kidney. However, current data suggest a complex and direct role for WNK s in the physiology of bone. The WNK s 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 + −K + −2Cl − cotransporter 1 in vascular smooth muscle cells. The WNK s and many of the cation‐coupled Cl − 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. 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.