Document Detail

CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship.
MedLine Citation:
PMID:  7683773     Owner:  NLM     Status:  MEDLINE    
In cystic fibrosis (CF), numerous epithelial cell functions are abnormal, including Cl- conductance, sodium absorption, mucin sulphation and enzyme secretion. Although the CF gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), functions as a small linear Cl- channel, it is difficult to attribute such pleiotropic disease manifestations solely to a defect in Cl- conductance. This has led to speculation that CFTR regulates the activity of other proteins. One possible example is the protein kinase A activation of outward rectifying Cl- channels (ORCC), which is defective in membrane patches excised from CF cells. Whether CFTR regulates the activity of an independent anion channel is debatable, because ORCC occur exclusively in excised membrane patches and could be an excision-induced molecular derivative of CFTR. 'Knockout' mice that lack CFTR provide a means to define the relationship between CFTR and ORCC. Here we report that ORCC are present in CFTR(-/-) mouse nasal epithelial cells and thus cannot be a derivative of the CFTR molecule. Also ORCC were regulated by protein kinase A in membrane patches from normal but not CFTR(-/-) cells. These observations are the first, to our knowledge definitive demonstration that CFTR regulates the activity of another protein.
S E Gabriel; L L Clarke; R C Boucher; M J Stutts
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature     Volume:  363     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1993 May 
Date Detail:
Created Date:  1993-06-10     Completed Date:  1993-06-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  263-8     Citation Subset:  IM    
Department of Medicine, University of North Carolina, Chapel Hill 27599-7020.
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MeSH Terms
3T3 Cells
Cells, Cultured
Chloride Channels
Chlorides / metabolism*
Cyclic AMP / metabolism
Cystic Fibrosis / metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator
Forskolin / pharmacology
Ion Channels / metabolism*
Membrane Potentials
Membrane Proteins / metabolism*
Protein Kinases / metabolism
Reg. No./Substance:
0/CFTR protein, human; 0/Chloride Channels; 0/Chlorides; 0/Ion Channels; 0/Membrane Proteins; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 2.7.-/Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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