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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2003-8-6
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pubmed:abstractText |
Dynamic regulation of ion channels is critical for maintaining fluid balance in epithelial tissues. Cystic fibrosis, a genetic disease characterized by impaired fluid transport in epithelial tissues, is caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity. Recent studies have shown that binding of PSD-95/Dlg/ZO-1 (PDZ) domain proteins to CFTR is important for retaining it at the apical membrane and for regulating its channel activity. Here, we describe a phosphorylation mechanism that regulates CFTR channel activity, which is mediated by PDZ domains. The Na+/H+ exchanger regulatory factor (NHERF) binds to CFTR and increases its open probability (Po). Protein kinase C disrupts the stimulatory effect of NHERF on CFTR channel Po. Phosphorylation by PKC of Ser-162 in the PDZ2 domain of NHERF is critical for this functional effect. Furthermore, a mutation in PDZ2 that mimics phosphorylation decreases CFTR binding and disrupts the ability of NHERF PDZ1-2 to stimulate CFTR channel Po. Our results identify a role for PKC and suggest that phosphorylation of NHERF PDZ2 domain may be an important mechanism for regulating CFTR channel activity.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10446210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10499588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10562288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10600390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10731148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10748023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10852925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-10859298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11007883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11046132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11051556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11099500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11158634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11165256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11283303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11304524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11456497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11573007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11707463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11882663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-11956211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-12075354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-12167629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-2447784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-2827498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-7686146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-8893032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9030559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9074797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9096337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9336840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9613608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9671706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9677412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9769419,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12881487-9922375
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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/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/CFTR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter,
http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9620-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12881487-Amino Acid Sequence,
pubmed-meshheading:12881487-Animals,
pubmed-meshheading:12881487-Aspartic Acid,
pubmed-meshheading:12881487-CHO Cells,
pubmed-meshheading:12881487-Cricetinae,
pubmed-meshheading:12881487-Cross-Linking Reagents,
pubmed-meshheading:12881487-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:12881487-Dose-Response Relationship, Drug,
pubmed-meshheading:12881487-Electrophysiology,
pubmed-meshheading:12881487-Epitopes,
pubmed-meshheading:12881487-Humans,
pubmed-meshheading:12881487-Ions,
pubmed-meshheading:12881487-Molecular Sequence Data,
pubmed-meshheading:12881487-Mutation,
pubmed-meshheading:12881487-Nerve Tissue Proteins,
pubmed-meshheading:12881487-Phosphorylation,
pubmed-meshheading:12881487-Precipitin Tests,
pubmed-meshheading:12881487-Protein Kinase C,
pubmed-meshheading:12881487-Protein Structure, Tertiary,
pubmed-meshheading:12881487-Sequence Homology, Amino Acid,
pubmed-meshheading:12881487-Serine,
pubmed-meshheading:12881487-Signal Transduction,
pubmed-meshheading:12881487-Sodium-Hydrogen Antiporter
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pubmed:year |
2003
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pubmed:articleTitle |
A kinase-regulated mechanism controls CFTR channel gating by disrupting bivalent PDZ domain interactions.
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pubmed:affiliation |
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
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pubmed:publicationType |
Journal Article
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