Regulation of CFTR channel gating.
Findings outlined here support a complex model for the regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel gating that incorporates incremental protein kinase A (PKA) phosphorylation of CFTR at multiple sites which, in turn, differentially control the activity of CFTR's two nucleotide-binding domains (NBDs). The NBDs are functionally distinct: only one can respond to the non-hydrolyzable ATP analogue AMP-PNP, and then only after ATP has acted at the other. Moreover, the nature of the responses to AMP-PNP, and to the inorganic phosphate analogue orthovanadate, argues that ATP hydrolysis normally occurs at both NBDs, at one to initiate channel opening and at the other to initiate closing.
Gadsby
D C
DC
Laboratory of Cardiac/Membrane Physiology, Rockefeller University, New York, NY 10021, USA.
Hwang
T C
TC
Baukrowitz
T
T
Nagel
G
G
Horie
M
M
Nairn
A C
AC
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006168:Guinea Pigs; D015640:Ion Channel Gating; D008958:Models, Molecular; D019319:Okadaic Acid; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation
D018118:Chloride Channels; D004988:Ethers, Cyclic; D019319:Okadaic Acid; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases