Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel

Peter M Snyder; Diane R Olson; Brittany C Thomas

doi:10.1074/jbc.C100623200

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Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel

Journal article

Open access

Peer reviewed

Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel

Peter M Snyder, Diane R Olson and Brittany C Thomas

The Journal of biological chemistry, Vol.277(1), pp.5-8

01/04/2002

DOI: 10.1074/jbc.C100623200

PMID: 11696533

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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.

Phosphorylation

Endosomal Sorting Complexes Required for Transport

Protein-Serine-Threonine Kinases - physiology

Sodium Channels - physiology

Sodium - metabolism

Nuclear Proteins

Immediate-Early Proteins

Ubiquitin-Protein Ligases

Epithelial Sodium Channels

Animals

Calcium-Binding Proteins - physiology

Nedd4 Ubiquitin Protein Ligases

Ligases - physiology

Sodium Channel Blockers

COS Cells

Details

Title: Subtitle: Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel
Creators: Peter M Snyder - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. psynder@blue.weeg.uiowa.edu
Diane R Olson
Brittany C Thomas
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(1), pp.5-8
DOI: 10.1074/jbc.C100623200
PMID: 11696533
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL58812 / NHLBI NIH HHS DK52617 / NIDDK NIH HHS HL55006 / NHLBI NIH HHS HL03575 / NHLBI NIH HHS HL61781 / NHLBI NIH HHS
Language: English
Date published: 01/04/2002
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
Record Identifier: 9984025321902771

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