{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T07:51:23Z","timestamp":1760255483133},"reference-count":84,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:00:00Z","timestamp":1384992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p>Identified over a decade ago, the with\u2010no\u2010lysine[K] kinases (<jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>s) have been the subsequent focus of intense research into the renal handling of Na<jats:sup>+<\/jats:sup>, Cl<jats:sup>\u2212<\/jats:sup> and K<jats:sup>+<\/jats:sup> and several rare monogenetic diseases. However, the potential extrarenal roles for <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>s have been less well explored.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca<jats:sup>2+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content><jats:sub>4<\/jats:sub><jats:sup>3\u2212<\/jats:sup> homeostasis, which were originally assumed to be an indirect effect through the kidney. However, current data suggest a complex and direct role for <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>s in the physiology of bone.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>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<jats:sup>+<\/jats:sup>\u2212K<jats:sup>+<\/jats:sup>\u22122Cl<jats:sup>\u2212<\/jats:sup> cotransporter 1 in vascular smooth muscle cells.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>s and many of the cation\u2010coupled Cl<jats:sup>\u2212<\/jats:sup> cotransporters they regulate are highly expressed in the central nervous system and recent work suggests that <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content> dysfunction may have a role in the development of autism, schizophrenia and hereditary sensory and autonomic neuropathy Type 2.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Finally, the <jats:styled-content style=\"fixed-case\">WNK<\/jats:styled-content>\u2013sterile 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.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12108","type":"journal-article","created":{"date-parts":[[2013,5,11]],"date-time":"2013-05-11T11:12:38Z","timestamp":1368270758000},"page":"885-894","source":"Crossref","is-referenced-by-count":11,"title":["Extrarenal roles of the with\u2010no\u2010lysine[<scp>K<\/scp>] kinases (<scp>WNK<\/scp>s)"],"prefix":"10.1111","volume":"40","author":[{"given":"Keith","family":"Siew","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Unit Department of Medicine University of Cambridge Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M","family":"O'Shaughnessy","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Department of Medicine University of Cambridge Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.22.16795"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204726"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062844"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1964.tb115766.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.1970.19.4.287"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1986.tb00358.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1978.03630280069022"},{"key":"e_1_2_6_9_1","first-page":"161","article-title":"Familiar hyperkalaemic acidosis","volume":"54","author":"Licht JH","year":"1985","journal-title":"Q. 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