Wang S, Yue H, Derin R B, Guggino W B, Li M
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cell. 2000 Sep 29;103(1):169-79. doi: 10.1016/s0092-8674(00)00096-9.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a chloride channel protein that belongs to the superfamily of ATP binding cassette (ABC) transporters. Phosphorylation by protein kinase A in the presence of ATP activates the CFTR-mediated chloride conductance of the apical membranes. We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces. CAP70 consists of four PDZ domains, three of which are capable of binding to the CFTR C terminus. Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity. Thus, the CFTR channel can be switched to a more active conducting state via a modification of intermolecular CFTR-CFTR contact that is enhanced by an accessory protein.
囊性纤维化跨膜传导调节因子（CFTR）基因编码一种氯化物通道蛋白，该蛋白属于ATP结合盒（ABC）转运体超家族。在ATP存在的情况下，蛋白激酶A的磷酸化作用激活了顶端膜上CFTR介导的氯化物传导。我们鉴定出一种新型的亲水性CFTR结合蛋白CAP70，它也集中在顶端表面。CAP70由四个PDZ结构域组成，其中三个能够与CFTR的C末端结合。通过多价CAP70或二价单克隆抗体经由细胞质C末端结合连接至少两个CFTR分子可增强CFTR氯化物通道活性。因此，CFTR通道可以通过修饰分子间CFTR-CFTR接触而转换为更活跃的传导状态，而这种修饰会因一种辅助蛋白而增强。
