Regulation of absorption by phosphorylation of CFTR.
In contrast to fluid secretion which in many tissues is well known to be regulated by phosphorylation, little is known of phosphorylation regulation of electrolyte absorption. It is now well established that CFTR (cystic fibrosis transmembrane regulator) is a Cl- channel which is activated by phosphorylation. The human eccrine sweat duct is an absorptive epithelium which expresses relatively large amounts of CFTR. We find that the Cl- conductance (GCl) expressed in the isolated, microperfused sweat duct is also dependent upon phosphorylation activation which can be mediated via cAMP. The activation is Mg2+ dependent, Ca2+ independent, and inhibited by the kinase inhibitor staurosporine. Deactivation appears to occur via endogenous phosphatases that can be inhibited by okadaic acid. We surmise that phosphorylation regulation of CFTR GCl is an important mechanism for shifting Cl- absorption efficiently between electroconductive and carrier mediated transport.
Quinton
P M
PM
Division of Biomedical Sciences, University of California, Riverside 92521, USA.
Reddy
M M
MM
D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004848:Epithelium; D006801:Humans; D017136:Ion Transport; D008565:Membrane Proteins / Q000502:physiology*; D008958:Models, Molecular; D010766:Phosphorylation
C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017868:Cyclic AMP-Dependent Protein Kinases