| http://purl.uniprot.org/citations/25330774 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25330774 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25330774 | http://www.w3.org/2000/01/rdf-schema#comment | "The major cystic fibrosis causing mutation, F508del-CFTR (where CFTR is cystic fibrosis transmembrane conductance regulator), impairs biosynthetic maturation of the CFTR protein, limiting its expression as a phosphorylation-dependent channel on the cell surface. The maturation defect can be partially rescued by low-temperature (27°C) cell culture conditions or small-molecule corrector compounds. Following its partial rescue, the open probability of F508del-CFTR is enhanced by the potentiator compound, VX-770. However, the channel activity of rescued F508del-CFTR remains less than that of the Wt-CFTR protein in the presence of VX-770. In this study, we asked if there are allosteric effects of F508del on the phosphorylation-regulated R domain. To identify defects in the R domain, we compared the phosphorylation status at protein kinase A sites in the R domain of Wt and F508del-CFTR. Here we show that phosphorylation of Ser-660, quantified by SRM-MS, is reduced in F508del-CFTR. Although the generation of a phosphomimic at this site (substituting aspartic acid for serine) did not modify the maturation defect, it did enhance F508del-CFTR channel function after pharmacological rescue with corrector VX-809, and treatment with the potentiator, VX-770. These findings support the concept that defective phosphorylation of F508del-CFTR partially accounts for its altered channel activity at the cell surface."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.org/dc/terms/identifier | "doi:10.1002/pmic.201400218"xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.org/dc/terms/identifier | "doi:10.1002/pmic.201400218"xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Bear C.E."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Bear C.E."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Chin S."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Chin S."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Ramjeesingh M."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Ramjeesingh M."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Taylor P."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Taylor P."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Du K."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Du K."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Moran M.F."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Moran M.F."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Yeger H."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Yeger H."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Ahmadi S."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Ahmadi S."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Huan L.J."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Huan L.J."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Molinski S."xsd:string |
| http://purl.uniprot.org/citations/25330774 | http://purl.uniprot.org/core/author | "Molinski S."xsd:string |