Publication Date:
1999-10-16
Description:
The cystic fibrosis gene encodes a chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A-dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH(2)-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail, which is a potential target for physiologic and pharmacologic modulators of this ion channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naren, A P -- Cormet-Boyaka, E -- Fu, J -- Villain, M -- Blalock, J E -- Quick, M W -- Kirk, K L -- DA10509/DA/NIDA NIH HHS/ -- DK50830/DK/NIDDK NIH HHS/ -- DK51868/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):544-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521352" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/metabolism
;
Amino Acid Sequence
;
Amino Acid Substitution
;
Animals
;
COS Cells
;
Cyclic AMP/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Cystic Fibrosis Transmembrane Conductance
;
Regulator/*chemistry/genetics/*metabolism
;
DNA Mutational Analysis
;
Humans
;
*Ion Channel Gating
;
Molecular Sequence Data
;
Mutation
;
Oocytes
;
Patch-Clamp Techniques
;
Phosphorylation
;
Protein Structure, Secondary
;
Recombinant Fusion Proteins/metabolism
;
Xenopus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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