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proteins. Page last changed on 14 Mar 2013.
WNK lysine deficient protein kinase 4
WNK4
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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Papers on
WNK4
An inducible transgenic mouse model for familial hypertension with hyperkalaemia (Gordon's syndrome or pseudohypoaldosteronism type II).
New
Cambridge, United Kingdom. In Clin Sci (lond), 01 Jul 2013
Mutations in the novel serine/threonine WNK [With No lysine (=K)] kinases WNK1 and WNK4 cause PHAII (pseudohypoaldosteronism type II or Gordon's syndrome), a rare monogenic syndrome which causes hypertension and hyperkalaemia on a background of a normal glomerular filtration rate.
Impaired KLHL3-Mediated Ubiquitination of WNK4 Causes Human Hypertension.
New
Tokyo, Japan. In Cell Rep, 27 Mar 2013
Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level.
The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms; disease-causing mutations in KLHL3 and WNK4 disrupt interaction.
New
In Biochem J, 06 Mar 2013
Interestingly, the equivalent region in WNK4 encompasses residues that are mutated in Gordon syndrome patients.
Regulation of WNK4 gene transcription in the kidneys.
New
Shenyang, China. In Genet Mol Res, 04 Feb 2013
With-no-lysine (K) kinase-4 (WNK4) is a newly cloned kinase-encoding gene that plays a crucial role in the maintenance of electrolyte homeostasis.
WNK Signaling Is Involved in Neural Development via Lhx8/Awh Expression.
New
Tokyo, Japan. In Plos One, Dec 2012
Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension.
Mechanisms of sodium-chloride cotransporter modulation by angiotensin II.
Review
New
Mexico City, Mexico. In Curr Opin Nephrol Hypertens, Sep 2012
Recent evidence suggests that these effects are achieved through modulation of the With No Lysine kinase 4 (WNK4) and Ste20-related, proline-alanine-rich kinase (SPAK) pathway.
Pathophysiology of salt sensitivity hypertension.
Review
New
Tokyo, Japan. In Ann Med, Jun 2012
Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension.
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.
New
Impact
Paris, France. In Nat Genet, Apr 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.
Pathogenesis of pseudohypoaldosteronism type 2 by WNK1 mutations.
Review
Paris, France. In Curr Opin Nephrol Hypertens, 2012
WNK1 and WNK4 are two of the genes mutated in PHA2 patients.
Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).
Review
Edmonton, Canada. In Pflugers Arch, 2011
Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation.
The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension.
Impact
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.
Antagonistic regulation of cystic fibrosis transmembrane conductance regulator cell surface expression by protein kinases WNK4 and spleen tyrosine kinase.
GeneRIF
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.
WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism.
GeneRIF
Wenzhou, China. In Am J Physiol Renal Physiol, 2011
WNK4 WT inhibits Maxi K activity by reducing Maxi K protein at the membrane, but the inhibition is not due to an increase in clathrin-mediated endocytosis of Maxi K, but likely due to enhancing its lysosomal degradation.
Immunolocalization of WNK4 in mouse kidney.
GeneRIF
Tokyo, Japan. In Histochem Cell Biol, 2011
Immunolocalization of WNK4 in mouse kidney.
Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature.
GeneRIF
Seoul, South Korea. In Proc Natl Acad Sci U S A, 2011
results define a previously undescribed function of WNK4 and reveal a unique therapeutic target to control blood pressure in WNK4-related hypertension
Renal nerves, WNK4, glucocorticoids, and salt transport.
Impact
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.
Impact
GeneRIF
Tokyo, Japan. In Nat Med, 2011
salt loading suppressed renal WNK4 expression, activated the Na(+)-Cl(-) cotransporter and induced salt-dependent hypertension
Familial renal tubular acidosis.
Review
Boston, United States. In J Nephrol, 2010
Hyperkalemic RTA accompanied by hypertension (pseudohypoaldosteronism type 2 [PHA2]) is caused by dominant gain-of-function mutations in the kinases WNK1 and WNK4.
Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A/+) knockin mouse model.
Impact
Tokyo, Japan. In Cell Metab, 2007
WNK1 and WNK4 mutations have been reported to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension.
