Extrarenal roles of the with-no-lysine[K] kinases (WNKs).

Abstract

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(+) , Cl(-) and K(+) and several rare monogenetic diseases. However, the potential extrarenal roles for WNKs have been less well explored. Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca(2+) and PO4 (3-) 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. 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(+) -K(+) -2Cl(-) cotransporter 1 in vascular smooth muscle cells. The WNKs 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.

• Authors: Keith Siew, Kevin M O'Shaughnessy
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 40 Issue 12 Pg. 885-94 (Dec 2013) ISSN: 1440-1681 [Electronic] Australia
• PMID: 23662678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2013 Wiley Publishing Asia Pty Ltd.

Chemical References

• Intracellular Signaling Peptides and Proteins
• Minor Histocompatibility Antigens
• Protein Serine-Threonine Kinases
• WNK Lysine-Deficient Protein Kinase 1
• WNK1 protein, human
• WNK4 protein, human

Topics

• Autistic Disorder (enzymology)
• Bone and Bones (enzymology)
• Cardiovascular System (enzymology)
• Central Nervous System (enzymology)
• Homeostasis (physiology)
• Humans
• Hypertension (enzymology)
• Immune System (enzymology)
• Intracellular Signaling Peptides and Proteins (genetics, physiology)
• Minor Histocompatibility Antigens
• Protein Serine-Threonine Kinases (genetics, physiology)
• WNK Lysine-Deficient Protein Kinase 1