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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0023689,
umls-concept:C0041538,
umls-concept:C0090388,
umls-concept:C0185117,
umls-concept:C0221908,
umls-concept:C0439799,
umls-concept:C0597484,
umls-concept:C1417660,
umls-concept:C1704675,
umls-concept:C2911684
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pubmed:issue |
13
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
The ubiquitin E3 protein ligase Nedd4-2 is a physiological regulator of the epithelial sodium channel ENaC, which is essential for transepithelial Na+ transport and is linked to Liddle's syndrome, an autosomal dominant disorder of human salt-sensitive hypertension. Nedd4-2 function is negatively regulated by phosphorylation via a serum- and glucocorticoid-inducible protein kinase (Sgk1), which serves as a mechanism to inhibit the ubiquitination-dependent degradation of ENaC. We report here that 14-3-3 proteins participate in this regulatory process through a direct interaction with a phosphorylated form of human Nedd4-2 (a human gene product of KIAA0439, termed hNedd4-2). The interaction is dependent on Sgk1-catalyzed phosphorylation of hNedd4-2 at Ser-468. We found that this interaction preserved the activity of the Sgk1-stimulated ENaC-dependent Na+ current while disrupting the interaction decreased ENaC density on the Xenopus laevis oocytes surface possibly by enhancing Nedd4-2-mediated ubiquitination that leads to ENaC degradation. Our findings suggest that 14-3-3 proteins modulate the cell surface density of ENaC cooperatively with Sgk1 kinase by maintaining hNedd4-2 in an inactive phosphorylated state.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endosomal Sorting Complexes...,
http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nedd4 ubiquitin protein ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/serum-glucocorticoid regulated...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13187-94
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15677482-14-3-3 Proteins,
pubmed-meshheading:15677482-Animals,
pubmed-meshheading:15677482-Catalysis,
pubmed-meshheading:15677482-Cattle,
pubmed-meshheading:15677482-Cell Line,
pubmed-meshheading:15677482-Cell Membrane,
pubmed-meshheading:15677482-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15677482-Electrophysiology,
pubmed-meshheading:15677482-Endosomal Sorting Complexes Required for Transport,
pubmed-meshheading:15677482-Epithelial Sodium Channel,
pubmed-meshheading:15677482-Genes, Dominant,
pubmed-meshheading:15677482-Glutathione Transferase,
pubmed-meshheading:15677482-Humans,
pubmed-meshheading:15677482-Immediate-Early Proteins,
pubmed-meshheading:15677482-Nuclear Proteins,
pubmed-meshheading:15677482-Oocytes,
pubmed-meshheading:15677482-PC12 Cells,
pubmed-meshheading:15677482-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15677482-Phosphorylation,
pubmed-meshheading:15677482-Plasmids,
pubmed-meshheading:15677482-Protein Binding,
pubmed-meshheading:15677482-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15677482-Rats,
pubmed-meshheading:15677482-Serine,
pubmed-meshheading:15677482-Silver Staining,
pubmed-meshheading:15677482-Sodium,
pubmed-meshheading:15677482-Sodium Channels,
pubmed-meshheading:15677482-Time Factors,
pubmed-meshheading:15677482-Ubiquitin,
pubmed-meshheading:15677482-Ubiquitin-Protein Ligases,
pubmed-meshheading:15677482-Xenopus,
pubmed-meshheading:15677482-Xenopus laevis
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pubmed:year |
2005
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pubmed:articleTitle |
14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase.
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pubmed:affiliation |
Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Tokyo 192-0397, Japan. ichimura@mial.comp.metro-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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