Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium channel regulation.
Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium channel regulation.
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DOI：
10.1371/journal.pone.0012163
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发表时间：
2010-08-13
期刊：
影响因子：
3.7
通讯作者：
McDonald FJ
中科院分区：
文献类型：
--
作者：
Wiemuth D;Lott JS;Ly K;Ke Y;Teesdale-Spittle P;Snyder PM;McDonald FJ
The epithelial sodium channel (ENaC) is an integral component of the pathway for Na+ absorption in epithelial cells. The ubiquitin ligases Nedd4 and Nedd4-2 bind to ENaC and decrease its activity. Conversely, Serum- and Glucocorticoid regulated Kinase-1 (SGK1), a downstream mediator of aldosterone, increases ENaC activity. This effect is at least partly mediated by direct interaction between SGK and Nedd4-2. SGK binds both Nedd4 and Nedd4-2, but it is only able to phosphorylate Nedd4-2. Phosphorylation of Nedd4-2 reduces its ability to bind to ENaC, due to the interaction of phosphorylated Nedd4-2 with 14-3-3 proteins, and hence increases ENaC activity. WW-domains in Nedd4-like proteins bind PY-motifs (PPXY) present in ENaC subunits, and SGK also has a PY-motif. Here we show that single or tandem WW-domains of Nedd4 and Nedd4-2 mediate binding to SGK and that different WW-domains of Nedd4 and Nedd4-2 are involved. Our data also show that WW-domains 2 and 3 of Nedd4-2 mediate the interaction with SGK in a cooperative manner, that activated SGK has increased affinity for the WW-domains of Nedd4-2 in vitro, and a greater stimulatory effect on ENaC Na+ transport compared to wildtype SGK. Further, SGK lacking a PY motif failed to stimulate ENaC activity in the presence of Nedd4-2. Binding of Nedd4-2 WW-domains to SGK is necessary for SGK-induced ENaC activity.
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影响因子：
4.1
作者：
Lott, JS;Coddington-Lawson, SJ;McDonald, FJ
通讯作者：
McDonald, FJ
影响因子：
4.8
作者：
Goulet, CC;Volk, KA;Snyder, PM
通讯作者：
Snyder, PM
DOI：
10.1073/pnas.96.5.2514
发表时间：
1999-03-02
影响因子：
11.1
作者：
Chen, SY;Bhargava, A;Pearce, D
通讯作者：
Pearce, D
影响因子：
10.8
作者：
Boehmer, C;Wilhelm, V;Lang, F
通讯作者：
Lang, F
影响因子：
--
作者：
SHEPPARD, DN;CARSON, MR;WELSH, MJ
通讯作者：
WELSH, MJ