WNK1 activates SGK1 to regulate the epithelial sodium channel

Bing E. Xu, Steve Stippec, Po Yin Chu, Ahmed Lazrak, Xin Ji Li, Byung Hoon Lee, Jessie M. English, Bernardo Ortega, Chou Long Huang, Melanie H. Cobb

Research output: Contribution to journalArticle

135 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)10315-10320
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number29
DOIs
StatePublished - Jul 19 2005

Fingerprint

Epithelial Sodium Channels
Pseudohypoaldosteronism
Hypertension
Lysine
Ions
Ubiquitin-Protein Ligases
Protein-Serine-Threonine Kinases
Protein Kinases
Glucocorticoids
Permeability
Phosphotransferases
Serum

Keywords

  • Ion transport
  • Nedd4-2
  • Pseudohypoaldosteronism type II

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

WNK1 activates SGK1 to regulate the epithelial sodium channel. / Xu, Bing E.; Stippec, Steve; Chu, Po Yin; Lazrak, Ahmed; Li, Xin Ji; Lee, Byung Hoon; English, Jessie M.; Ortega, Bernardo; Huang, Chou Long; Cobb, Melanie H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 29, 19.07.2005, p. 10315-10320.

Research output: Contribution to journalArticle

Xu, Bing E. ; Stippec, Steve ; Chu, Po Yin ; Lazrak, Ahmed ; Li, Xin Ji ; Lee, Byung Hoon ; English, Jessie M. ; Ortega, Bernardo ; Huang, Chou Long ; Cobb, Melanie H. / WNK1 activates SGK1 to regulate the epithelial sodium channel. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 29. pp. 10315-10320.
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AU - Xu, Bing E.

AU - Stippec, Steve

AU - Chu, Po Yin

AU - Lazrak, Ahmed

AU - Li, Xin Ji

AU - Lee, Byung Hoon

AU - English, Jessie M.

AU - Ortega, Bernardo

AU - Huang, Chou Long

AU - Cobb, Melanie H.

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