Premium
The secret life of CFTR as a calcium‐activated chloride channel
Author(s) -
Billet Arnaud,
Hanrahan John W.
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.261909
Subject(s) - chloride channel , adenylyl cyclase , chemistry , cystic fibrosis transmembrane conductance regulator , phosphorylation , ion channel , protein kinase a , phosphatase , cystic fibrosis , purinergic receptor , microbiology and biotechnology , protein tyrosine phosphatase , g protein , signal transduction , receptor , biochemistry , medicine , biology , gene
Abstract cAMP‐stimulated anion conductance is defective in cystic fibrosis (CF). The regulatory domain of CFTR, the anion channel protein encoded by the CF gene, possesses an unusually high density of consensus sequences for phosphorylation by protein kinase A (14 in a stretch of <200 amino acids). Thus it is not surprising that CFTR is viewed primarily as a cAMP‐stimulated anion channel, and most studies have focused on this mode of activation. However, there is growing evidence that CFTR also responds to Ca 2+ ‐mobilizing secretagogues and contributes substantially to cholinergic and purinergic responses in native tissues. G protein‐coupled receptors that signal through G αq can stimulate CFTR channels by activating Ca 2+ ‐dependent adenylyl cyclase and tyrosine kinases, and also by inhibiting protein phosphatase type 2A. Here we review evidence for these novel mechanisms of CFTR activation and discuss how they may help explain previous observations.