The cystic fibrosis transmembrane conductance regulator (CFTR)- cAMP- stimulated chloride ion channel expressed in the apical membrane of epithelial cells; critical for transepithelial salt and fluid transport. Two homologous motifs, each consisting of six transmembrane helices followed by a cytoplasmic ATP binding domain.  Two motifs connected by regulatory domain.  PKA activates the channel by direct phosphorylation, but PKC does not activate CFTR substantially, but seems to increase responsiveness to PKA. Binding of PDZ domains of the Na+/H+ exchanger regulatory factor (NHERF, also known as EBP50) directly regulates CFTR channel activity. The binding and cross-linking of two C-terminal tails of CFTR by two PDZ domains in a bivalent molecule allosterically enhances CFTR gating, whereas PDZ domain binding in the absence of cross-linking does not.