Abstract
Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channel by Its R Domain
Highlights
Sequence and Boundaries of the R Domain The R domain was originally defined as those residues encoded by exon 13 (Fig. 1) [1]
The most striking feature of the R domain is the presence of multiple consensus protein kinase (PKA) phosphorylation sites that are highly conserved across species (Fig. 1)
When CFTR is phosphorylated in cells by addition of cAMP agonists, detectable phosphorylation is limited to Ser-660, Ser-700, Ser-737, Ser-795, and Ser-813 [13, 14, 17]
Summary
PKA is the primary kinase that phosphorylates CFTR, protein kinase C, cGMP-dependent protein kinase, and tyrosine phosphorylation can stimulate channel activity [2, 3]. Mutation of either Ser-660 or Ser-813 reduced the open state probability (Po) of CFTR studied under several conditions [20, 21, 23]. These two residues play key stimulatory roles. Cell-free patches, the S737A mutant reduced Po [20], but in Xenopus oocytes and epithelia, the S737A mutant increased cAMP-stimulated current [21, 23] We speculate that these differences may be because of loss of kinases, phosphatases, or associated molecules after membrane excision. These data suggest either concomitant or sequential phosphorylation events may be required
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call