PHOSPHORYLATION-DEPENDENT BLOCK OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CHLORIDE CHANNEL BY EXOGENOUS-R DOMAIN PROTEIN

The cystic fibrosis transmembrane conductance regulator (CFTR) constit utes a linear conductance chloride channel, which is regulated by cAMP -dependent protein kinase phosphorylation at multiple sites located in the intracellular regulatory (R) domain, Studies in a lipid bilayer s ystem, reported here, provide evidence for the control of CFTR chlorid e channel by its R domain, The exogenous R domain protein (encoded by exon 13 plus 85 base pairs of exon 14) interacted specifically with th e CFTR molecule and inhibited the chloride conductance in a phosphoryl ation-dependent manner. Only the unphosphorylated R domain protein blo cked the CFTR channel, Such functional interaction suggests that the p utative gating particle of the CFTR chloride channel resides in the R domain.