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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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Top mentioned proteins: SPAK, CAN, V1a, OSR1, ROMK
Papers on WNK4
Mechanisms of Angiotensin II Stimulation of NCC Are Time-Dependent in mDCT15 Cells.
New
Hoover et al., Chicago, United States. In Am J Physiol Renal Physiol, 28 Feb 2015
Angiotensin II (ANGII) has been implicated as a switch which turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4.
Kelch-Like Protein 2 Mediates Angiotensin II-With No Lysine 3 Signaling in the Regulation of Vascular Tonus.
New
Uchida et al., Tokyo, Japan. In J Am Soc Nephrol, 02 Feb 2015
UNASSIGNED: Recently, the kelch-like protein 3 (KLHL3)-Cullin3 complex was identified as an E3 ubiquitin ligase for with no lysine (WNK) kinases, and the impaired ubiquitination of WNK4 causes pseudohypoaldosteronism type II (PHAII), a hereditary hypertensive disease.
The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride.
New
Gamba et al., Mexico. In J Am Soc Nephrol, Jan 2015
UNASSIGNED: It is widely recognized that the phenotype of familial hyperkalemic hypertension is mainly a consequence of increased activity of the renal Na(+)-Cl(-) cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4.
Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways.
New
Fujita et al., Tokyo, Japan. In Am J Physiol Renal Physiol, Jan 2015
Recent studies revealed the involvement of two important signaling pathways in renal tubules that play key roles in electrolyte balance and the maintenance of normal blood pressure: the β2 adrenergic stimulant-GR-WNK4-NCC pathway, which is active in distal convoluted tubules 1 (DCT1); and the Rac1-MR pathway, which is active in distal convoluted tubules 2 (DCT2), connecting tubules (CNT), and collecting ducts (CD).
Gordon Syndrome: a continuing story.
New
O'Shaughnessy, Cambridge, United Kingdom. In Pediatr Nephrol, Jan 2015
In 2001, mutations in genes encoding two serine/threonine kinases, WNK1 and WNK4, were identified as causing GS.
Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems.
Review
New
Fujita, Tokyo, Japan. In J Am Soc Nephrol, Jun 2014
Furthermore, these studies point to crucial roles for the Rac1-mineralocorticoid receptor-NCC/ENaC and the renal β-adrenergic stimulant-glucocorticoid receptor-WNK4-NCC pathways in certain rodent models of salt-sensitive hypertension.
Insights in cullin 3/WNK4 and its relationship to blood pressure regulation and electrolyte homeostasis.
Review
New
Pedraza-Chaverri et al., Mexico. In Cell Signal, Jun 2014
One of the most important systems for protein degradation is the ubiquitin-proteasome system (UPS).
Interacting influence of diuretics and diet on BK channel-regulated K homeostasis.
Review
New
Sansom et al., Omaha, United States. In Curr Opin Pharmacol, Apr 2014
In distal nephron cells, membrane BK-α expression is inhibited by WNK4 in in vitro expression systems, indicating a role in the hyperkalemic phenotype in patients with familial hyperkalemic hypertension type 2 (FHHt2).
Molecular insights from dysregulation of the thiazide-sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide-induced hyponatraemia.
Review
O'Shaughnessy et al., Nottingham, United Kingdom. In Clin Exp Pharmacol Physiol, 2013
with-no-lysine(K) kinase 1 (WNK1), WNK4, kelch-like family member 3 (KLHL3) and cullin 3 (CUL3)] can cause the phenotype of GS.
Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia.
Impact
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).
Effects of angiotensin II on kinase-mediated sodium and potassium transport in the distal nephron.
Review
Hoorn et al., Rotterdam, Netherlands. In Curr Opin Nephrol Hypertens, 2013
RECENT FINDINGS: Ang II can activate the sodium chloride cotransporter (NCC) through phosphorylation by Ste20-related, proline-alanine rich kinase (SPAK), an effect that is independent of aldosterone but dependent on with no lysine kinase 4 (WNK4).
Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process.
GeneRIF
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.
Impact
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.
GeneRIF
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.
GeneRIF
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.
GeneRIF
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.
Impact
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.
GeneRIF
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.
Impact
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.
Impact
GeneRIF
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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