Due to necessary maintenance, Xenbase will be unavailable December 24-30, 2014. We apologize for the inconvenience.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-7965
EMBO J. December 17, 2001; 20 (24): 7052-9.

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

Debonneville C , Flores SY , Kamynina E , Plant PJ , Tauxe C , Thomas MA , Münster C , Chraïbi A , Pratt JH , Horisberger JD , Pearce D , Loffing J , Staub O .


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.

PubMed ID: 11742982
PMC ID: PMC125341
Article link: EMBO J.

Genes referenced: avp nedd4 nedd4l sgk1
Antibodies referenced:
Morpholinos referenced:

My Xenbase: [ Log-in / Register ]
version: [3.3.1]


Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556