Journal article
WNK1 activates SGK1 to regulate the epithelial sodium channel
Proceedings of the National Academy of Sciences - PNAS, Vol.102(29), pp.10315-10320
07/08/2005
DOI: 10.1073/pnas.0504422102
PMCID: PMC1177404
PMID: 16006511
Abstract
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.
Details
- Title: Subtitle
- WNK1 activates SGK1 to regulate the epithelial sodium channel
- Creators
- Bing-e Xu - The University of Texas Southwestern Medical CenterSteve Stippec - The University of Texas Southwestern Medical CenterPo-Yin Chu - The University of Texas Southwestern Medical CenterAhmed Lazrak - The University of Texas Southwestern Medical CenterXin-Ji Li - The University of Texas Southwestern Medical CenterByung-Hoon Lee - The University of Texas Southwestern Medical CenterJessie M. English - The University of Texas Southwestern Medical CenterBernardo Ortega - The University of Texas Southwestern Medical CenterChou-Long Huang - The University of Texas Southwestern Medical CenterMelanie H. Cobb - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.102(29), pp.10315-10320
- Publisher
- National Academy of Sciences
- DOI
- 10.1073/pnas.0504422102
- PMID
- 16006511
- PMCID
- PMC1177404
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Language
- English
- Date published
- 07/08/2005
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359694902771
Metrics
16 Record Views