Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a chloride channel protein that belongs to the superfamily of ATP binding cassette (ABC) transporters. Phosphorylation by protein kinase A in the presence of ATP activates the CFTR-mediated chloride conductance of the apical membranes. We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces. CAP70 consists of four PDZ domains, three of which are capable of binding to the CFTR C terminus. Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity. Thus, the CFTR channel can be switched to a more active conducting state via a modification of intermolecular CFTR-CFTR contact that is enhanced by an accessory protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / physiology
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / isolation & purification*
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Carrier Proteins / metabolism
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Carrier Proteins / pharmacology
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Cell Extracts / analysis
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Cell Extracts / chemistry
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Cell Membrane / metabolism
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Cell Membrane / ultrastructure
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Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
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Cystic Fibrosis Transmembrane Conductance Regulator / drug effects
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Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
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Intestine, Small / cytology
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Intestine, Small / metabolism
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Kidney / cytology
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Kidney / metabolism
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Membrane Proteins*
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Mice
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Models, Biological
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Molecular Sequence Data
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Protein Structure, Tertiary / drug effects*
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Protein Structure, Tertiary / physiology
Substances
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Carrier Proteins
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Cell Extracts
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Membrane Proteins
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Cystic Fibrosis Transmembrane Conductance Regulator