CFTR Chloride Channel Regulation by an Interdomain Interaction

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Science  15 Oct 1999:
Vol. 286, Issue 5439, pp. 544-548
DOI: 10.1126/science.286.5439.544

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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.

  • * These authors contributed equally to this report.

  • To whom correspondence should be addressed. E-mail: kirk{at}

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