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Science 286 (5439): 544-548

Copyright © 1999 by the American Association for the Advancement of Science

CFTR Chloride Channel Regulation by an Interdomain Interaction

Anjaparavanda P. Naren, 1* Estelle Cormet-Boyaka, 1* Jian Fu, 1 Matteo Villain, 1 J. Edwin Blalock, 1 Michael W. Quick, 12 Kevin L. Kirk 12dagger

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 NH2-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.

1 Department of Physiology and Biophysics,
2 Department of Neurobiology, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: kirk{at}phybio.bhs.uab.edu


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