title: Phosphorylation-dependent block of cystic fibrosis transmembrane conductance regulator chloride channel by exogenous R domain protein.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) constitutes a linear conductance chloride channel, which is regulated by cAMP-dependent protein kinase phosphorylation at multiple sites located in the intracellular regulatory (R) domain. Studies in a lipid bilayer system, reported here, provide evidence for the control of CFTR chloride channel by its R domain. The exogenous R domain protein (encoded by exon 13 plus 85 base pairs of exon 14) interacted specifically with the CFTR molecule and inhibited the chloride conductance in a phosphorylation-dependent manner. Only the unphosphorylated R domain protein blocked the CFTR channel. Such functional interaction suggests that the putative gating particle of the CFTR chloride channel resides in the R domain.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: J E
authors.initials: JE
authors.lastname: Tasch
authors.forename: T
authors.initials: T
authors.lastname: Tao
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: M L
authors.initials: ML
authors.lastname: Drumm
authors.forename: P B
authors.initials: PB
authors.lastname: Davis
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D018076:DNA, Complementary; D005091:Exons; D015870:Gene Expression; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D007668:Kidney; D008564:Membrane Potentials; D008861:Microsomes / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000502:physiology; D011544:Pseudogenes; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D018076:DNA, Complementary; D015221:Potassium Channels; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017868:Cyclic AMP-Dependent Protein Kinases