Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression

Details

Serval ID
serval:BIB_15C020BBD53F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression
Journal
EMBO Journal
Author(s)
Debonneville  C., Flores  S. Y., Kamynina  E., Plant  P. J., Tauxe  C., Thomas  M. A., Munster  C., Chraibi  A., Pratt  J. H., Horisberger  J. D., Pearce  D., Loffing  J., Staub  O.
ISSN
0261-4189 (Print)
Publication state
Published
Issued date
12/2001
Volume
20
Number
24
Pages
7052-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 17
Abstract
The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.
Keywords
Amino Acid Sequence Animals Calcium-Binding Proteins/*metabolism Cell Line/metabolism Epithelial Sodium Channel Immediate-Early Proteins Ligases/*metabolism *Nuclear Proteins Oocytes/metabolism Phosphorylation Protein Binding Protein-Serine-Threonine Kinases/*metabolism Sodium Channels/*metabolism Ubiquitin/metabolism *Ubiquitin-Protein Ligases Xenopus laevis
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 12:37
Last modification date
20/08/2019 12:44
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