title: The secret life of CFTR as a calcium-activated chloride channel.
abstract: cAMP-stimulated anion conductance is defective in cystic fibrosis (CF). The regulatory domain of CFTR, the anion channel protein encoded by the CF gene, possesses an unusually high density of consensus sequences for phosphorylation by protein kinase A (14 in a stretch of <200 amino acids). Thus it is not surprising that CFTR is viewed primarily as a cAMP-stimulated anion channel, and most studies have focused on this mode of activation. However, there is growing evidence that CFTR also responds to Ca(2+)-mobilizing secretagogues and contributes substantially to cholinergic and purinergic responses in native tissues. G protein-coupled receptors that signal through Gαq can stimulate CFTR channels by activating Ca(2+)-dependent adenylyl cyclase and tyrosine kinases, and also by inhibiting protein phosphatase type 2A. Here we review evidence for these novel mechanisms of CFTR activation and discuss how they may help explain previous observations.
authors: J. W. Hanrahan: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada H3G 1Y6. john.hanrahan@mcgill.ca.
authors: Arnaud
authors: A
authors: Billet
authors: John W
authors: JW
authors: Hanrahan
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D000262:Adenylyl Cyclases; D002118:Calcium
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