Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3

Détails

ID Serval
serval:BIB_34B25F1EFFD7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3
Périodique
Molecular Endocrinology
Auteur⸱e⸱s
Bhalla  V., Daidie  D., Li  H., Pao  A. C., LaGrange  L. P., Wang  J., Vandewalle  A., Stockand  J. D., Staub  O., Pearce  D.
ISSN
0888-8809 (Print)
Statut éditorial
Publié
Date de publication
12/2005
Volume
19
Numéro
12
Pages
3073-84
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
Serum- and glucocorticoid-regulated kinase 1 (SGK1) is an aldosterone-regulated early response gene product that regulates the activity of several ion transport proteins, most notably that of the epithelial sodium channel (ENaC). Recent evidence has established that SGK1 phosphorylates and inhibits Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), a ubiquitin ligase that decreases cell surface expression of the channel and possibly stimulates its degradation. The mechanistic basis for this SGK1-induced Nedd4-2 inhibition is currently unknown. In this study we show that SGK1-mediated phosphorylation of Nedd4-2 induces its interaction with members of the 14-3-3 family of regulatory proteins. Through functional characterization of Nedd4-2-mutant proteins, we demonstrate that this interaction is required for SGK1-mediated inhibition of Nedd4-2. The concerted action of SGK1 and 14-3-3 appears to disrupt Nedd4-2-mediated ubiquitination of ENaC, thus providing a mechanism by which SGK1 modulates the ENaC-mediated Na(+) current. Finally, the expression pattern of 14-3-3 is also consistent with a functional role in distal nephron Na(+) transport. These results demonstrate a novel, physiologically significant role for 14-3-3 proteins in modulating ubiquitin ligase-dependent pathways in the control of epithelial ion transport.
Mots-clé
14-3-3 Proteins/*metabolism Animals Epithelial Cells/metabolism Epithelial Sodium Channel Humans Immediate-Early Proteins/*metabolism Ion Transport Kidney Tubules/cytology Kidney Tubules, Collecting/metabolism Mice Mutation Phosphorylation Protein-Serine-Threonine Kinases/*metabolism Rats Rats, Sprague-Dawley Sodium/metabolism Sodium Channels/metabolism/*physiology Ubiquitin/metabolism Ubiquitin-Protein Ligases/antagonists & inhibitors/genetics/*metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 13:03
Dernière modification de la notice
20/08/2019 13:21
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