Regulatory crosstalk by protein kinases on CFTR trafficking and activity

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e., channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.Work supported by the Portuguese Fundação para a Ciência e Tecnologia (fellowship grant SFRH/BSAB/105741/2014—to CF, grant PTDC/SAU-ORG/119782/2010—to PJ, and centre grant UID/MULTI/04046/2013—to BioISI); Gilead Génese PGG/039/2014 and ERS Romain Pauwels 2012 (to CF); CFF SWIATE14P0 (to AS); NIH NIDDK P30 072506 Basic and Translational Studies of Cystic Fibrosis (P&F to AS)