Phosphorylation-regulated Cl- channel in CHO cells stably expressing the cystic fibrosis gene.
A cyclic AMP-stimulated chloride conductance appears when the cystic fibrosis gene is expressed in non-epithelial cells by infection with recombinant viruses. Cyclic AMP-stimulated conductance in this system is mediated by the same ohmic, low-conductance Cl- channel as in human secretory epithelia, but control of this channel by phosphorylation has not been directly demonstrated. Here we report the appearance of the low-conductance Cl- channel in Chinese hamster ovary cells after stable transfection with the cystic fibrosis gene. The channel is regulated on-cell by membrane-permeant analogues of cAMP and off-cell by protein kinases A and C and by alkaline phosphatase. These results are further evidence that the cystic fibrosis transmembrane regulator is a Cl- channel which can be activated by specific phosphorylation events and inactivated by dephosphorylation; they reveal an unsuspected synergism between converging kinase regulatory pathways.
Tabcharani
J A
JA
Department of Physiology, McGill University, Montreal, Québec, Canada.
Chang
X B
XB
Riordan
J R
JR
Hanrahan
J W
JW
D000818:Animals; D002460:Cell Line; D018118:Chloride Channels; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D011494:Protein Kinases