Molecular physiology of the WNK kinases - PubMed (original) (raw)
Review
Molecular physiology of the WNK kinases
Kristopher T Kahle et al. Annu Rev Physiol. 2008.
Abstract
Mutations in the serine-threonine kinases WNK1 and WNK4 cause a Mendelian disease featuring hypertension and hyperkalemia. In vitro and in vivo studies have revealed that these proteins are molecular switches that have discrete functional states that impart different effects on downstream ion channels, transporters, and the paracellular pathway. These effects enable the distal nephron to allow either maximal NaCl reabsorption or maximal K+ secretion in response to hypovolemia or hyperkalemia, respectively. The related kinase WNK3 has reciprocal actions on the primary mediators of cellular Cl(-) influx and efflux, effects that can serve to regulate cell volume during growth and in response to osmotic stress as well as to modulate neuronal responses to GABA. These findings define a versatile new family of kinases that coordinate the activities of diverse ion transport pathways to achieve and maintain fluid and electrolyte homeostasis.
Similar articles
- WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1).
Leng Q, Kahle KT, Rinehart J, MacGregor GG, Wilson FH, Canessa CM, Lifton RP, Hebert SC. Leng Q, et al. J Physiol. 2006 Mar 1;571(Pt 2):275-86. doi: 10.1113/jphysiol.2005.102202. Epub 2005 Dec 15. J Physiol. 2006. PMID: 16357011 Free PMC article. - WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis.
Rinehart J, Kahle KT, de Los Heros P, Vazquez N, Meade P, Wilson FH, Hebert SC, Gimenez I, Gamba G, Lifton RP. Rinehart J, et al. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16777-82. doi: 10.1073/pnas.0508303102. Epub 2005 Nov 7. Proc Natl Acad Sci U S A. 2005. PMID: 16275913 Free PMC article. - Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension.
Gamba G. Gamba G. Am J Physiol Renal Physiol. 2005 Feb;288(2):F245-52. doi: 10.1152/ajprenal.00311.2004. Am J Physiol Renal Physiol. 2005. PMID: 15637347 Review. - WNK kinases regulate thiazide-sensitive Na-Cl cotransport.
Yang CL, Angell J, Mitchell R, Ellison DH. Yang CL, et al. J Clin Invest. 2003 Apr;111(7):1039-45. doi: 10.1172/JCI17443. J Clin Invest. 2003. PMID: 12671053 Free PMC article. - Regulation of diverse ion transport pathways by WNK4 kinase: a novel molecular switch.
Kahle KT, Wilson FH, Lifton RP. Kahle KT, et al. Trends Endocrinol Metab. 2005 Apr;16(3):98-103. doi: 10.1016/j.tem.2005.02.012. Trends Endocrinol Metab. 2005. PMID: 15808806 Review.
Cited by
- Ion and solute transport by Prestin in Drosophila and Anopheles.
Hirata T, Czapar A, Brin L, Haritonova A, Bondeson DP, Linser P, Cabrero P, Thompson J, Dow JA, Romero MF. Hirata T, et al. J Insect Physiol. 2012 Apr;58(4):563-9. doi: 10.1016/j.jinsphys.2012.01.009. Epub 2012 Jan 30. J Insect Physiol. 2012. PMID: 22321763 Free PMC article. - Basolateral Kir4.1 activity in the distal convoluted tubule regulates K secretion by determining NaCl cotransporter activity.
Wang WH. Wang WH. Curr Opin Nephrol Hypertens. 2016 Sep;25(5):429-35. doi: 10.1097/MNH.0000000000000248. Curr Opin Nephrol Hypertens. 2016. PMID: 27306796 Free PMC article. Review. - Regulated endocytosis of NCC.
Mount DB. Mount DB. Am J Physiol Renal Physiol. 2010 Aug;299(2):F297-9. doi: 10.1152/ajprenal.00280.2010. Epub 2010 May 26. Am J Physiol Renal Physiol. 2010. PMID: 20504880 Free PMC article. No abstract available. - Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.
Mu S, Shimosawa T, Ogura S, Wang H, Uetake Y, Kawakami-Mori F, Marumo T, Yatomi Y, Geller DS, Tanaka H, Fujita T. Mu S, et al. Nat Med. 2011 May;17(5):573-80. doi: 10.1038/nm.2337. Epub 2011 Apr 17. Nat Med. 2011. PMID: 21499270 - C. elegans STK39/SPAK ortholog-mediated inhibition of ClC anion channel activity is regulated by WNK-independent ERK kinase signaling.
Falin RA, Miyazaki H, Strange K. Falin RA, et al. Am J Physiol Cell Physiol. 2011 Mar;300(3):C624-35. doi: 10.1152/ajpcell.00343.2010. Epub 2010 Dec 15. Am J Physiol Cell Physiol. 2011. PMID: 21160027 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical