Phosphorylation-dependent block of cystic fibrosis transmembrane conductance regulator chloride channel by exogenous R domain protein.
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.
Ma
J
J
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Tasch
J E
JE
Tao
T
T
Zhao
J
J
Xie
J
J
Drumm
M L
ML
Davis
P B
PB
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
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