Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The CFTR gene, located on chromosome 7q31, was identified in 1989. Genomic DNA probes from the chromosomal region (DNA sequences that showed high homology across species) were used to screen a cDNA...

In the more than 10 years that have elapsed since the identification by positional cloning of the cystic fibrosis gene, 1-3 the gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), has been implicated in a variety of functional roles in cells. 4-10 Of these,...

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is tightly regulated by the opposing actions of protein kinases and phosphatases. Its phosphorylation and activation by protein kinases A (PKA) and C (PKC) have been studied in some detail but phosphatase...

In epithelial tissues of cystic fibrosis patients, the secretory Cl- transport is impaired, while the absorptive Na + transport is enhanced. The disease causing cystic fibrosis transmembrane conductance regulator (CFTR) is a protein expressed primarily in luminal membranes of secretory and...

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) controls salt and water transport across epithelial tissues. CFTR serves this role primarily by functioning as a cyclic AMP-activated chloride channel at the lumen-facing, or apical, membranes of epithelial cells that line the...

The major pulmonary pathology of cystic fibrosis (CF) is caused by colonization of the airways with Pseudomonas aeruginosa and other bacteria. The airways are lined with a thin film of liquid, the airway surface liquid ( ASL), that in health is ~10 μm deep. How does reduced CFTR function...

The lung disease of cystic fibrosis (CF) is characterized by a self-sustaining cycle of airway obstruction, infection and inflammation that accounts for the majority of morbidity and mortality. Bacteria in the CF airway incite a vigorous inflammatory response that is more pernicious than...

The precise functional defects and mechanisms linking mutations in CFTR to disease phenotype are not well understood. Although CFTR serves as a cAMP activated Clchannel, it has also been implicated in other cellular processes including regulation of ion transport (e.g., through the epithelial...

The search for compounds to rescue the biosynthesis of DF508-CFTR has become a major goal of the Cystic Fibrosis research community. The Cystic Fibrosis Foundation has partnered with several pharmaceutical companies in an effort to achieve this goal. Hundreds of thousands of compounds have...