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WNK lysine deficient protein kinase 4

This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009] (from NCBI)
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Top mentioned proteins: SPAK, CAN, V1a, OSR1, ROMK
Papers on WNK4
Periodic hypokalaemic polymyopathy in Burmese and closely related cats: A review including the latest genetic data.
Gandolfi et al., Sydney, Australia. In J Feline Med Surg, 31 May 2015
RECENT ADVANCES AND FUTURE PROSPECTS: Recent molecular genetics research has identified a single nonsense mutation in the gene (WNK4) coding for lysine-deficient 4 protein kinase, an enzyme present primarily in the distal nephron.
The renal sodium chloride co-transporter, NCC, is unchanged in the mid pregnant rat and decreased in the late pregnant rat despite avid renal sodium retention.
Baylis et al., Virginia, South Africa. In Am J Physiol Renal Physiol, 29 May 2015
We also measured mRNA expression of NCC, and members of SPAK/NCC regulatory kinase network, SGK1, total WNK1, WNK3, and WNK4.
A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.
Cheng et al., Dallas, United States. In Pflugers Arch, 24 May 2015
Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia.
Hypercalciuria in Familial Hyperkalemia and Hypertension with KLHL3 Mutations.
Hanukoglu et al., Israel. In Nephron, 22 May 2015
Mutations in WNK4 and WNK1 were found initially, and recently additional mutations were found in two genes, KLHL3 and CUL3, which are components of the Ubiquitin system.
KLHL3 regulates paracellular chloride transport in the kidney by ubiquitination of claudin-8.
Hou et al., Saint Louis, United States. In Proc Natl Acad Sci U S A, 07 May 2015
Genetic linkage studies and exome sequencing have identified four genes-with no lysine kinase 1 (wnk1), wnk4, Kelch-like 3 (KLHL3), and Cullin 3 (Cul3)-mutations of which all caused PHA-II phenotypes.
Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK).
Wang et al., West Haven, United States. In Proc Natl Acad Sci U S A, 07 May 2015
With-no-lysine kinase 4 (WNK4) inhibits the activity of the potassium channel KCNJ1 (ROMK) in the distal nephron, thereby contributing to the maintenance of potassium homeostasis.
Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways.
Fujita et al., Tokyo, Japan. In Am J Physiol Renal Physiol, Apr 2015
β2-Adrenergic stimulation due to increased renal sympathetic activity in obesity- and salt-induced hypertension suppresses histone deacetylase 8 activity via cAMP/PKA signaling, increasing the accessibility of GRs to the negative GR response element in the WNK4 promoter.
Regulation of blood pressure and renal electrolyte balance by Cullin-RING ligases.
Uchida, Tokyo, Japan. In Curr Opin Nephrol Hypertens, Sep 2014
The PHAII-causing mutations in WNK4, KLHL3, and Cullin-3 result in the decreased ubiquitination and increased abundance of WNK4 in the kidney, thereby activating the thiazide-sensitive NaCl cotransporter and causing PHAII.
Disorders of aldosterone synthesis, secretion, and cellular function.
Root, Saint Petersburg, United States. In Curr Opin Pediatr, Aug 2014
Secondary hypoaldosteronism (pseudohypoaldosteronism) occurs as a consequence of mutations in genes encoding the mineralocorticoid receptor (MR), the three subunits of the aldosterone-responsive, amiloride-sensitive nonvoltage-gated sodium channel encoded by SCNN1A, SCNN1B, and SCNN1G, the gene that regulates posttranslational phosphorylation (encoded by WNK4) of the thiazide-sensitive sodium chloride cotransporter encoded by SLC12A3, and those that regulate phosphorylation and ubiquitination of cofactors encoded by WNK1, KLH3, and CUL3 that affect WNK4 function.
Calcineurin inhibitors and hypertension: a role for pharmacogenetics?
Hoorn et al., Rotterdam, Netherlands. In Pharmacogenomics, Jun 2014
Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension.
Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia.
Lifton et al., New Haven, United States. In Cell Metab, 2013
In volume depletion, angiotensin II and WNK4 signaling decrease MR(S843-P) levels, whereas hyperkalemia increases MR(S843-P).
Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process.
Gamba et al., Mexico. In Proc Natl Acad Sci U S A, 2012
Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process.
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.
Jeunemaitre et al., Paris, France. In Nat Genet, 2012
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron.
Disease-causing mutations in the acidic motif of WNK4 impair the sensitivity of WNK4 kinase to calcium ions.
Peng et al., Birmingham, United States. In Biochem Biophys Res Commun, 2012
these results suggest that these PHAII-causing mutations disrupt a Ca(2+)-sensing mechanism around the acidic motif necessary for the regulation of WNK4 kinase activity by Ca(2+) ions.
WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway.
Cai et al., Atlanta, United States. In Am J Physiol Renal Physiol, 2012
data suggest that WNK4 inhibits NCC protein through activating the MAPK ERK1/2 signaling pathway.
Antagonistic regulation of cystic fibrosis transmembrane conductance regulator cell surface expression by protein kinases WNK4 and spleen tyrosine kinase.
Jordan et al., Lisbon, Portugal. In Mol Cell Biol, 2011
Results show that Tyr512 phosphorylation is a novel signal regulating the prevalence of CFTR at the cell surface and that WNK4 and Syk perform an antagonistic role in this process.
The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension.
Ellison et al., Portland, United States. In Nat Med, 2011
In wild-type mice, the CNI tacrolimus caused salt-sensitive hypertension and increased the abundance of phosphorylated NCC and the NCC-regulatory kinases WNK3, WNK4 and SPAK.
Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response.
Hui et al., Beijing, China. In Clin Biochem, 2011
hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.
Renal nerves, WNK4, glucocorticoids, and salt transport.
Brooks et al., Portland, United States. In Cell Metab, 2011
A study in Nature Medicine (Mu et al., 2011) shows that dietary salt excess, coupled with β-adrenergic stimulation, increases arterial pressure via glucocorticoid receptors and WNK4, suggesting interactions between these systems in the pathogenesis of hypertension.
Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.
Fujita et al., Tokyo, Japan. In Nat Med, 2011
salt loading suppressed renal WNK4 expression, activated the Na(+)-Cl(-) cotransporter and induced salt-dependent hypertension
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