WNK1 Activates SGK1 to Regulate the Epithelial Sodium Channel

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 und...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-07, Vol.102 (29), p.10315-10320
Main Authors: Bing-e Xu, Stippec, Steve, Chu, Po-Yin, Lazrak, Ahmed, Li, Xin-Ji, Lee, Byung-Hoon, English, Jessie M., Ortega, Bernardo, Huang, Chou-Long, Cobb, Melanie H., Garbers, David L.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Blood pressure
Cells, Cultured
CHO Cells
Cricetinae
Cricetulus
Endosomal Sorting Complexes Required for Transport
Enzyme Activation - physiology
Epithelial Sodium Channels
Gene expression
Gene expression regulation
HEK293 cells
Humans
Hypertension
Immediate-Early Proteins - metabolism
Immunoblotting
Immunoprecipitation
Intracellular Signaling Peptides and Proteins
Ions
Minor Histocompatibility Antigens
Nedd4 Ubiquitin Protein Ligases
Oocytes
Patch-Clamp Techniques
Phosphorylation
Protein-Serine-Threonine Kinases - metabolism
Proteins
Pseudohypoaldosteronism - metabolism
Pseudohypoaldosteronism - physiopathology
Sodium
Sodium channels
Sodium Channels - metabolism
Two-Hybrid System Techniques
Ubiquitin-Protein Ligases - metabolism
WNK Lysine-Deficient Protein Kinase 1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0504422102