title: (WNK)ing at death: With-no-lysine (Wnk) kinases in neuropathies and neuronal survival.
abstract: Members of With-no-lysine (WNK) family of serine-threonine kinase are key regulators of chloride ion transport in diverse cell types, controlling the activity and the surface expression of cation-chloride (Na(+)/K(+)-Cl(-)) co-transporters. Mutations in WNK1 and WNK4 are linked to a hereditary form of hypertension, and WNKs have been extensively investigated pertaining to their roles in renal epithelial ion homeostasis. However, some members of the WNK family and their splice isoforms are also expressed in the mammalian brain, and have been implicated in aspects of hereditary neuropathy as well as neuronal and glial survival. WNK2, which is exclusively enriched in neurons, is well known as an anti-proliferative tumor suppressor. WNK3, on the other hand, appears to promote cell survival as its inhibition enhances neuronal apoptosis. However, loss of WNK3 has been recently shown to reduce ischemia-associated brain damage. In this review, I surveyed the potentially context-dependent roles of WNKs in neurological disorders and neuronal survival.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore. Electronic address: bchtbl@nus.edu.sg.
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009422:Nervous System Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics
chemical_list: D028021:Sodium-Potassium-Chloride Symporters; D017346:Protein Serine-Threonine Kinases; D008239:Lysine
keywords: K(+)-Cl(−)co-transporter 2 (KCC2); Na(+)/K(+)-Cl(−) cotransporter 1 (NKCC1); Neuronal death; Tumor suppressor; With-no-lysine(K) (WNK) kinase