文章基本信息

标题：WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl−-transporting epithelia
本地全文：下载
作者：Keith A. Choate ; Kristopher T. Kahle ; Frederick H. Wilson 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：2
页码：663-668
DOI：10.1073/pnas.242728499
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mutations in WNK1 and WNK4, genes encoding members of a novel family of serine-threonine kinases, have recently been shown to cause pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder featuring hypertension, hyperkalemia, and renal tubular acidosis. The localization of these kinases in the distal nephron and the Cl- dependence of these phenotypes suggest that these mutations increase renal Cl- reabsorption. Although WNK4 expression is limited to the kidney, WNK1 is expressed in many tissues. We have examined the distribution of WNK1 in these extrarenal tissues. Immunostaining using WNK1-specific antibodies demonstrated that WNK1 is not present in all cell types; rather, it is predominantly localized in polarized epithelia, including those lining the lumen of the hepatic biliary ducts, pancreatic ducts, epididymis, sweat ducts, colonic crypts, and gallbladder. WNK1 is also found in the basal layers of epidermis and throughout the esophageal epithelium. The subcellular localization of WNK1 varies among these epithelia. WNK1 is cytoplasmic in kidney, colon, gallbladder, sweat duct, skin, and esophagus; in contrast, it localizes to the lateral membrane in bile ducts, pancreatic ducts, and epididymis. These epithelia are all notable for their prominent role in Cl- flux. Moreover, these sites largely coincide with those involved in the pathology of cystic fibrosis, a disease characterized by deranged epithelial Cl- flux. Together with the known pathophysiology of PHAII, these findings suggest that WNK1 plays a general role in the regulation of epithelial Cl- flux, a finding that suggests the potential of new approaches to the selective modulation of these processes.
关键词：protein–serine–threonine kinases ‖ion transport‖cystic fibrosis‖ medical genetics