Nudge‐nudge, WNK ‐ WNK (kinases), say no more?

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WNK kinases, renal ion transport and hypertension.

Two members of a recently discovered family of protein kinases are the cause of an inherited disease known as pseudohypoaldosteronism type II (PHAII). These patients exhibit arterial hypertension together with hyperkalemia and metabolic acidosis. This is a mirror image of Gitelman disease that is due to inactivating mutations of the SLC12A3 gene that encodes the thiazide-sensitive Na(+):Cl(-) c...

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WNK kinases regulate thiazide-sensitive Na-Cl cotransport.

Pseudohypoaldosteronism type II (PHAII) is an autosomal dominant disorder of hyperkalemia and hypertension. Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease. WNK1 mutations are believed to increase WNK1 expression; the effect of WNK4 mutations remains unknown. The clinical phenotype of PHAII is opposite to Gitelman syndrome, a disease caused by dysfunction of ...

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WNK kinases influence TRPV4 channel function and localization.

TRPV4, a renally expressed nonselective cation channel of the transient receptor potential (TRP) family, is gated by hypotonicity. Kinases of the WNK family influence expression and function of the thiazide-sensitive Na+-Cl- cotransporter, and monogenic human hypertension has been linked to mutations in the gene coding for WNK4. Along with TRPV4, WNK isoforms are highly expressed in the distal ...

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Intersectin links WNK kinases to endocytosis of ROMK1.

With-no-lysine (WNK) kinases are a novel family of protein kinases characterized by an atypical placement of the catalytic lysine. Mutations of 2 family members, WNK1 and WNK4, cause pseudohypoaldosteronism type 2 (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. WNK1 and WNK4 stimulate clathrin-dependent endocytosis of renal outer medullar potassium 1 (ROMK1...

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WNK kinases, distal tubular ion handling and hypertension.

Familial hyperkalaemic hypertension (FHH) was originally described by Paver and Pauline in 1964 [1]. Also referred to as Gordon syndrome [2] or pseudohypoaldosteronism type 2 [3], the FHH syndromes are rare autosomal dominant diseases characterized by the unusual association of low renin hypertension with hyperkalaemia and metabolic acidosis despite normal glomerular filtration rate. These clin...

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ژورنال

عنوان ژورنال: New Phytologist

سال: 2018

ISSN: 0028-646X,1469-8137

DOI: 10.1111/nph.15276