Journal article
Nucleoside triphosphates are required to open the CFTR chloride channel
Cell (Cambridge), Vol.67(4), pp.775-784
11/15/1991
DOI: 10.1016/0092-8674(91)90072-7
PMID: 1718606
Abstract
The CFTR Cl− channel contains two predicted nucleotide-binding domains (NBD1 and NBD2); therefore, we examined the effect of ATP on channel activity. Once phosphorylated by cAMP-dependent protein kinase (PKA), channels required cytosolic ATP to open. Activation occurred by a PKA-independent mechanism. ATPγS substituted for ATP in PKA phosphorylation, but it did not open the channel. Several hydrolyzable nucleotides (ATP > GTP > ITP ≈ UTP > CTP) reversibly activated phosphorylated channels, but nonhydrolyzable analogs and Mg2+-free ATP did not. Studies of CFTR mutants indicated that ATP controls channel activity independent of the R domain and suggested that hydrolysis of ATP by NBD1 may be sufficient for channel opening. The finding that nucleoside triphosphates regulate CFTR begins to explain why CF-associated mutations in the NBDs block Cl− channel function.
Details
- Title: Subtitle
- Nucleoside triphosphates are required to open the CFTR chloride channel
- Creators
- Matthew P Anderson - Howard Hughes Medical Institute Department of Internal Medicine University of Iowa College of Medicine Iowa City, Iowa 52242 USAHerbert A Berger - Howard Hughes Medical Institute Department of Internal Medicine University of Iowa College of Medicine Iowa City, Iowa 52242 USADevra P Rich - Howard Hughes Medical Institute Department of Internal Medicine University of Iowa College of Medicine Iowa City, Iowa 52242 USARichard J Gregory - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701 USAAlan E Smith - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701 USAMichael J Welsh - Howard Hughes Medical Institute Department of Internal Medicine University of Iowa College of Medicine Iowa City, Iowa 52242 USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.67(4), pp.775-784
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0092-8674(91)90072-7
- PMID
- 1718606
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 11/15/1991
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020727902771
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