CFTR is a plasma membrane protein belonging to the superfamily of ABC transporters. CFTR works as an ion channel permeable to Cl-, bicarbonate, thiocyanate, and other anions. CFTR structure includes: transmembrane helices that form the conductive pathway and probably the gate; two NBDs, NBD1, and NBD2 that face the cytosolic side and dimerize by binding to two molecules of intracellular ATP; a cytosolic region, the R domain, not present in other ABC proteins, that is the site of cAMP-dependent phosphorylation. Intracellular cAMP elevation is the trigger for CFTR activation. Activation of CFTR requires phosphorylation by protein kinase A (PKA) at multiple sites located at the regulatory domain (RD). Because channel phosphorylation by PKA is mandatory for channel activity, CFTR channel is frequently defined as a ‘‘cAMP-activated channel’’. Protein kinase-C (PKC) dependent phosphorylation at multiple sites is necessary for complete PKA-dependent activation of CFTRLoss of CFTR function is the cause of the multiorgan defects that characterize cystic fibrosis (CF), a genetic disease due to CFTR gene mutations. CF manifestations include: progressive loss of respiratory function, pancreatic insufficiency, biliary cirrhosis, male infertility, and excessive salt loss by sweating.

References

1.Zegarra-Moran O,et al. Cell Mol Life Sci. 2017 Jan;74(1):117-128.
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