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Science 12 July 1991: Vol. 253. no. 5016, pp. 202 - 205 DOI: 10.1126/science.1712984
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Articles
Science, Vol 253, Issue 5016, 202-205
Copyright © 1991 by American Association for the Advancement of Science
Demonstration that CFTR is a chloride channel by alteration of its anion selectivity
MP Anderson,
RJ Gregory,
S Thompson,
DW Souza,
S Paul,
RC Mulligan,
AE Smith,
and
MJ Welsh
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.
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- Structure and Function of the CFTR Chloride Channel.
- D. N. SHEPPARD and M. J. WELSH (1999)
Physiol Rev
79, 23-45
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- CFTR: Mechanism of Anion Conduction.
- D. C. DAWSON, S. S. SMITH, and M. K. MANSOURA (1999)
Physiol Rev
79, 47-75
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- Control of CFTR Channel Gating by Phosphorylation and Nucleotide Hydrolysis.
- D. C. GADSBY and A. C. NAIRN (1999)
Physiol Rev
79, 77-107
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- Influence of Cell Polarity on Retrovirus-Mediated Gene Transfer to Differentiated Human Airway Epithelia.
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J. Virol.
72, 9818-9826
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- Tissue Distribution, Cellular Source, and Structural Analysis of Rat Immunoreactive Uroguanylin.
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Endocrinology
139, 5247-5254
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- Adrenergic stimulation of Na+ transport across alveolar epithelial cells involves activation of apical Cl- channels.
- X. Jiang, D. H. Ingbar, and S. M. O'Grady (1998)
Am J Physiol Cell Physiol
275, C1610-C1620
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- Acetylcholine-induced liquid secretion by bronchial epithelium: role of Cl- and HCO-3 transport.
- L. Trout, J. T. Gatzy, and S. T. Ballard (1998)
Am J Physiol Lung Cell Mol Physiol
275, L1095-L1099
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- Covalent Modification of the Nucleotide Binding Domains of Cystic Fibrosis Transmembrane Conductance Regulator.
- J. F. Cotten and M. J. Welsh (1998)
J. Biol. Chem.
273, 31873-31879
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- The Second Half of the Cystic Fibrosis Transmembrane Conductance Regulator Forms a Functional Chloride Channel.
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J. Biol. Chem.
273, 29373-29380
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- Cystic Fibrosis Transmembrane Conductance Regulator-associated ATP Release Is Controlled by a Chloride Sensor.
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J. Cell Biol.
143, 645-657
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- Non-pore lining amino acid side chains influence anion selectivity of the human CFTR Cl- channel expressed in mammalian cell lines.
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J. Physiol.
512, 1-16
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- Focus on "Exocytosis is not involved in activation of Cl- secretion via CFTR in Calu-3 airway epithelial cells".
- W. B. Guggino (1998)
Am J Physiol Cell Physiol
275, C911-C912
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- Characterization of an Allele-Nonspecific Intragenic Suppressor in the Yeast Plasma Membrane H+-ATPase Gene (PMA1).
- A. M. Maldonado, N. de la Fuente, and F. Portillo (1998)
Genetics
150, 11-19
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- Membrane Trafficking of the Cystic Fibrosis Gene Product, Cystic Fibrosis Transmembrane Conductance Regulator, Tagged with Green Fluorescent Protein in Madin-Darby Canine Kidney Cells.
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273, 21759-21768
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- Partial restoration of cAMP-stimulated CFTR chloride channel activity in Delta F508 cells by deoxyspergualin.
- C. Jiang, S. L. Fang, Y.-F. Xiao, S. P. O'Connor, S. G. Nadler, D. W. Lee, D. M. Jefferson, J. M. Kaplan, A. E. Smith, and S. H. Cheng (1998)
Am J Physiol Cell Physiol
275, C171-C178
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- Expression of a hypotonic swelling-activated Cl conductance during ontogeny of collecting duct epithelium.
- S. M. Huber and M. F. Horster (1998)
Am J Physiol Renal Physiol
275, F25-F32
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- Cl- transport by cystic fibrosis transmembrane conductance regulator (CFTR) contributes to the inhibition of epithelial Na+ channels (ENaCs) in Xenopus oocytes co-expressing CFTR and ENaC.
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J. Physiol.
508, 825-836
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- Regulation of chloride secretion across porcine endometrial epithelial cells by prostaglandin E2.
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J. Physiol.
508, 31-47
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- Sertoli cell expression of the cystic fibrosis transmembrane conductance regulator.
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Am J Physiol Cell Physiol
274, C922-C930
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- Arylaminobenzoate Block of the Cardiac Cyclic AMP-Dependent Chloride Current.
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Mol. Pharmacol.
53, 539-546
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