Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel

Seng H Cheng; Devra P Rich; John Marshall; Richard J Gregory; Michael J Welsh; Alan E Smith

doi:10.1016/0092-8674(91)90446-6

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Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel

Journal article

Peer reviewed

Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel

Seng H Cheng, Devra P Rich, John Marshall, Richard J Gregory, Michael J Welsh and Alan E Smith

Cell (Cambridge), Vol.66(5), pp.1027-1036

1991

DOI: 10.1016/0092-8674(91)90446-6

PMID: 1716180

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Abstract

CFTR, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to cAMP agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase A. The SPQ fluorescence assay revealed that mutagenesis of any one of these sites did not affect Cl − channel activity. Indeed, concomitant mutagenesis of three of the four sites still resulted in cAMP-responsive Cl − channel activity. However, mutagenesis of all four sites abolished the response. One interpretation of these results is that the CFTR Cl − channel is blocked by the R domain and that phosphorylation on serines by protein kinase A electrostatically repels the domain, allowing passage of Cl − The four phosphorylation events appear to be degenerate: no one site is essential for channel activity, and, at least in the case of serine 660, phosphorylation at one site alone is sufficient for regulation of Cl − channel activity.

Details

Title: Subtitle: Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel
Creators: Seng H Cheng - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701, USA
Devra P Rich - Howard Hughes Medical Institute and Department of Internal Medicine and Physiology and Biophysics University of Iowa College of Medicine Iowa City, Iowa 52242, USA
John Marshall - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701, USA
Richard J Gregory - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701, USA
Michael J Welsh - Howard Hughes Medical Institute and Department of Internal Medicine and Physiology and Biophysics University of Iowa College of Medicine Iowa City, Iowa 52242, USA
Alan E Smith - Genzyme Corporation One Mountain Road Framingham, Massachusetts 01701, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.66(5), pp.1027-1036
Publisher: Elsevier Inc
DOI: 10.1016/0092-8674(91)90446-6
PMID: 1716180
ISSN: 0092-8674
eISSN: 1097-4172
Language: English
Date published: 1991
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
Record Identifier: 9984020733902771

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