文章基本信息

标题：WNK1 activates SGK1 to regulate the epithelial sodium channel
本地全文：下载
作者：Bing-e Xu ; Steve Stippec ; Po-Yin Chu 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：2005
卷号：102
期号：29
页码：10315-10320
DOI：10.1073/pnas.0504422102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：WNK (with no lysine [K]) kinases are serine-threonine protein kinases with an atypical placement of the catalytic lysine. Intronic deletions increase the expression of WNK1 in humans and cause pseudohypoaldosteronism type II, a form of hypertension. WNKs have been linked to ion carriers, but the underlying regulatory mechanisms are unknown. Here, we report a mechanism for the control of ion permeability by WNK1. We show that WNK1 activates the serum- and glucocorticoid-inducible protein kinase SGK1, leading to activation of the epithelial sodium channel. Increased channel activity induced by WNK1 depends on SGK1 and the E3 ubiquitin ligase Nedd4-2. This finding provides compelling evidence that this molecular mechanism contributes to the pathogenesis of hypertension in pseudohypoaldosteronism type II caused by WNK1 and, possibly, in other forms of hypertension.
关键词：ion transport ; Nedd4-2 ; pseudohypoaldosteronism type II