TY - JOUR
T1 - CFTR chloride channel regulation by an interdomain interaction
AU - Naren, Anjaparavanda P.
AU - Cormet-Boyaka, Estelle
AU - Fu, Jian
AU - Villain, Matteo
AU - Blalock, J. Edwin
AU - Quick, Michael W.
AU - Kirk, Kevin L.
PY - 1999/10/15
Y1 - 1999/10/15
N2 - The cystic fibrosis gene encodes a chloride channel CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A-dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH2-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail which is a potential target for physiologic and pharmacologic modulators of this ion channel.
AB - The cystic fibrosis gene encodes a chloride channel CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A-dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH2-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail which is a potential target for physiologic and pharmacologic modulators of this ion channel.
UR - http://www.scopus.com/inward/record.url?scp=0033569511&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033569511&partnerID=8YFLogxK
U2 - 10.1126/science.286.5439.544
DO - 10.1126/science.286.5439.544
M3 - Article
C2 - 10521352
AN - SCOPUS:0033569511
SN - 0036-8075
VL - 286
SP - 544
EP - 548
JO - Science
JF - Science
IS - 5439
ER -