File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Phosphatase inhibitors activate normal and defective CFTR chloride channels

TitlePhosphatase inhibitors activate normal and defective CFTR chloride channels
Authors
Keywordscystic fibrosis transmembrane conductance regulator
rundown
Issue Date1994
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 1994, v. 91 n. 19, p. 9160-9164 How to Cite?
AbstractThe cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is regulated by phosphorylation and dephosphorylation at multiple sites. Although activation by protein kinases has been studied in some detail, the dephosphorylation step has received little attention. This report examines the mechanisms responsible for the dephosphorylation and spontaneous deactivation ('rundown') of CFTR chloride channels excised from transfected Chinese hamster ovary (CHO) and human airway epithelial cells. We report that the alkaline phosphate inhibitors bromotetramisole, 3-isobutyl-1- methylxanthine, theophylline, and vanadate slow the rundown of CFTR channel activity in excised membrane patches and reduce dephosphorylation of CFTR protein in isolated membranes. It was also found that in unstimulated cells, CFTR channels can be activated by exposure to phosphatase inhibitors alone. Most importantly, exposure of mammalian cells to phosphatase inhibitors alone activates CFTR channels that have disease-causing mutations, provided the mutant channels are present in the plasma membrane (R117H, G551D, and ΔF508 after cooling). These results suggest that CFTR dephosphorylation is dynamic and that membrane-associated phosphatase activity may be a potential therapeutic target for the treatment of cystic fibrosis.
Persistent Identifierhttp://hdl.handle.net/10722/44277
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBecq, Fen_HK
dc.contributor.authorJensen, TJen_HK
dc.contributor.authorChang, XBen_HK
dc.contributor.authorSavoia, Aen_HK
dc.contributor.authorRommens, JMen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorBuchwald, Men_HK
dc.contributor.authorRiordan, JRen_HK
dc.contributor.authorHanrahan, JWen_HK
dc.date.accessioned2007-09-12T03:50:28Z-
dc.date.available2007-09-12T03:50:28Z-
dc.date.issued1994en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1994, v. 91 n. 19, p. 9160-9164en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44277-
dc.description.abstractThe cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is regulated by phosphorylation and dephosphorylation at multiple sites. Although activation by protein kinases has been studied in some detail, the dephosphorylation step has received little attention. This report examines the mechanisms responsible for the dephosphorylation and spontaneous deactivation ('rundown') of CFTR chloride channels excised from transfected Chinese hamster ovary (CHO) and human airway epithelial cells. We report that the alkaline phosphate inhibitors bromotetramisole, 3-isobutyl-1- methylxanthine, theophylline, and vanadate slow the rundown of CFTR channel activity in excised membrane patches and reduce dephosphorylation of CFTR protein in isolated membranes. It was also found that in unstimulated cells, CFTR channels can be activated by exposure to phosphatase inhibitors alone. Most importantly, exposure of mammalian cells to phosphatase inhibitors alone activates CFTR channels that have disease-causing mutations, provided the mutant channels are present in the plasma membrane (R117H, G551D, and ΔF508 after cooling). These results suggest that CFTR dephosphorylation is dynamic and that membrane-associated phosphatase activity may be a potential therapeutic target for the treatment of cystic fibrosis.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectcystic fibrosis transmembrane conductance regulatoren_HK
dc.subjectrundownen_HK
dc.subject.meshRundownen_HK
dc.subject.meshCystic fibrosis transmembrane conductance regulatoren_HK
dc.subject.mesh1-methyl-3-isobutylxanthine - pharmacologyen_HK
dc.subject.meshChloride channels - drug effectsen_HK
dc.subject.meshPhosphoric monoester hydrolases - antagonists & inhibitorsen_HK
dc.titlePhosphatase inhibitors activate normal and defective CFTR chloride channelsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=91&issue=19&spage=9160&epage=9164&date=1994&atitle=Phosphatase+inhibitors+activate+normal+and+defective+CFTR+channelsen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1073/pnas.91.19.9160en_HK
dc.identifier.pmid7522329en_HK
dc.identifier.pmcidPMC44767-
dc.identifier.scopuseid_2-s2.0-0028577602en_HK
dc.identifier.volume91en_HK
dc.identifier.issue19en_HK
dc.identifier.spage9160en_HK
dc.identifier.epage9164en_HK
dc.identifier.isiWOS:A1994PG52100088-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBecq, F=7003512120en_HK
dc.identifier.scopusauthoridJensen, TJ=7401539543en_HK
dc.identifier.scopusauthoridChang, XB=7202486073en_HK
dc.identifier.scopusauthoridSavoia, A=7007026639en_HK
dc.identifier.scopusauthoridRommens, JM=7006884140en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridBuchwald, M=7006759922en_HK
dc.identifier.scopusauthoridRiordan, JR=7202229758en_HK
dc.identifier.scopusauthoridHanrahan, JW=7103386837en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats