Letter/Communication
Stimulation of CFTR activity by its phosphorylated R domain
Nature (London), Vol.389(6648), pp.294-296
09/18/1997
DOI: 10.1038/38514
PMID: 9305845
Abstract
Phosphorylation controls the activity of ion channels in many tissues. In epithelia, the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is activated by phosphorylation of serine residues in its regulatory (R) domain and then gated by binding and hydrolysis of ATP by the nucleotide-binding domains. Current models propose that the unphosphorylated R domain serves as an inhibitory particle that occludes the pore, much like the inhibitory 'ball' in Shaker K+ channels; presumably, phosphorylation relieves this inhibition. Here we test this by adding an R-domain peptide to a CFTR variant in which much of the R domain had been deleted (CFTR-ΔR/S660A): in contrast to predictions, we found that adding an unphosphorylated R domain to CFTR-ΔR/S660A did not inhibit activity, whereas a phosphorylated R-domain peptide stimulated activity. To investigate how phosphorylation controls activity, we studied channel gating and found that phosphorylation of the R domain increases the rate of channel opening by enhancing the sensitivity to ATP. Our results indicate that CFTR is regulated by a new mechanism in which phosphorylation of one domain stimulates the interaction of ATP with another domain, thereby increasing activity.
Details
- Title: Subtitle
- Stimulation of CFTR activity by its phosphorylated R domain
- Creators
- Michael C Winter - University of Iowa, Anatomy and Cell BiologyMichael J Welsh - University of Iowa, Internal Medicine
- Resource Type
- Letter/Communication
- Publication Details
- Nature (London), Vol.389(6648), pp.294-296
- DOI
- 10.1038/38514
- PMID
- 9305845
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 09/18/1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020769602771
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