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Cited by 381

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Serum and Glucocorticoid-regulated Kinase Modulates Nedd4-2-mediated Inhibition of the Epithelial Na+Channel

Snyder, Peter M., Olson, Diane R., Thomas, Brittany C.·2002·Journal of Biological Chemistry
DOI 10.1074/jbc.c100623200
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Abstract

The epithelial Na+ channel (ENaC) forms the pathway for Na+ absorption across epithelia, including the kidney collecting duct, where it plays a critical role in Na+ homeostasis and blood pressure control. Na+ absorption is regulated in part by mechanisms that control the expression of ENaC at the apical cell surface. Nedd4 family members (e.g. Nedd4, Nedd4-2) bind to the channel and decrease its surface expression by catalyzing its ubiquitination and degradation. Conversely, serum and glucocorticoid-regulated kinase (SGK), a downstream mediator of aldosterone, increases the expression of ENaC at the cell surface. Here we show that SGK and human Nedd4-2 (hNedd4-2) converge in a common pathway to regulate epithelial Na+ absorption. Consistent with this model, we found that SGK bound to hNedd4-2 and hNedd4. A PY motif in SGK mediated the interaction and was required for SGK to stimulate ENaC. SGK phosphorylated hNedd4-2 (but not hNedd4), altering hNedd4-2 function; phosphorylation reduced the binding of hNedd4-2 to alphaENaC, and hence, the hNedd4-2-mediated inhibition of Na+ absorption. These data suggest that SGK regulates epithelial Na+ absorption in part by modulating the function of hNedd4-2.

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Crossref · 10.1074/jbc.c100623200

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Citations

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Research works printed but not linked: 30

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Metadata

Authors
Snyder, P. M., Olson, D. R., & Thomas, B. C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-01
Volume
277
Issue
1
Pages
5-8
ISSN
0021-9258
DOI
10.1074/jbc.c100623200
Cited by
381
References
1
Language
en
Licence

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