Serine/threonine-protein kinase WNK3

Definition:

Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.; Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686, isoform 1 inhibits the activity of SLC12A3.

References:

[1]. F Veríssimo, et al. Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway. Oncogene. 2006 Jul 13;25(30):4172-82. [Content Brief]

[2]. Mark Glover, et al. Renal and brain isoforms of WNK3 have opposite effects on NCCT expression. J Am Soc Nephrol. 2009 Jun;20(6):1314-22. [Content Brief]

[3]. Silvia Cruz-Rangel, et al. Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011 Sep;301(3):C601-8. [Content Brief]

[4]. Chao-Ling Yang, et al. The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J Clin Invest. 2007 Nov;117(11):3403-11. [Content Brief]

[5]. Wei Zhang, et al. WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway. Am J Physiol Renal Physiol. 2008 Nov;295(5):F1472-84. [Content Brief]

[6]. Qiang Leng, et al. WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1). J Physiol. 2006 Mar 1;571(Pt 2):275-86. [Content Brief]

[7]. Kristopher T Kahle, et al. WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16783-8. [Content Brief]

[8]. Charles J Heise, et al. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010 Aug 13;285(33):25161-7. [Content Brief]

[9]. Jesse Rinehart, et al. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16777-82. [Content Brief]

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