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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2004-4-19
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pubmed:abstractText |
Based on the observation that the Na(+)/K(+)-ATPase alpha subunit contains two conserved caveolin-binding motifs, we hypothesized that clustering of the Na(+)/K(+)-ATPase and its partners in caveolae facilitates ouabain-activated signal transduction. Glutathione S-transferase pull-down assay showed that the Na(+)/K(+)-ATPase bound to the N terminus of caveolin-1. Significantly, ouabain regulated the interaction in a time- and dose-dependent manner and stimulated tyrosine phosphorylation of caveolin-1 in LLC-PK1 cells. When added to the isolated membrane fractions, ouabain increased tyrosine phosphorylation of proteins from the isolated caveolae but not other membrane fractions. Consistently, ouabain induced the formation of a Na(+)/K(+)-ATPase-Src-caveolin complex in the isolated caveolae preparations as it did in live cells. Finally, depletion of either cholesterol by methyl beta-cyclodextrin or caveolin-1 by siRNA significantly reduced the caveolar Na(+)/K(+)-ATPase and Src. Concomitantly, cholesterol depletion abolished ouabain-induced recruitment of Src to the Na(+)/K(+)-ATPase signaling complex. Like depletion of caveolin-1, it also blocked the effect of ouabain on ERKs, which was restored after cholesterol repletion. Clearly, the caveolar Na(+)/K(+)-ATPase represents the signaling pool of the pump that interacts with Src and transmits the ouabain signals.
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pubmed:grant |
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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/CAV1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caveolin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Caveolins,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ouabain,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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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 |
23
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17250-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14963033-Amino Acid Sequence,
pubmed-meshheading:14963033-Animals,
pubmed-meshheading:14963033-Caveolin 1,
pubmed-meshheading:14963033-Caveolins,
pubmed-meshheading:14963033-Cell Line,
pubmed-meshheading:14963033-Cell Membrane,
pubmed-meshheading:14963033-Cholesterol,
pubmed-meshheading:14963033-Dose-Response Relationship, Drug,
pubmed-meshheading:14963033-Enzyme Inhibitors,
pubmed-meshheading:14963033-Humans,
pubmed-meshheading:14963033-Mitogen-Activated Protein Kinases,
pubmed-meshheading:14963033-Molecular Sequence Data,
pubmed-meshheading:14963033-Ouabain,
pubmed-meshheading:14963033-Phosphorylation,
pubmed-meshheading:14963033-Precipitin Tests,
pubmed-meshheading:14963033-Protein Structure, Tertiary,
pubmed-meshheading:14963033-RNA, Small Interfering,
pubmed-meshheading:14963033-Sequence Homology, Amino Acid,
pubmed-meshheading:14963033-Signal Transduction,
pubmed-meshheading:14963033-Sodium-Potassium-Exchanging ATPase,
pubmed-meshheading:14963033-Swine,
pubmed-meshheading:14963033-Time Factors,
pubmed-meshheading:14963033-Tyrosine
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pubmed:year |
2004
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pubmed:articleTitle |
Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase.
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pubmed:affiliation |
Department of Pharmacology and Medicine, Medical College of Ohio, Toledo, Ohio 43614, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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