Abstract
We asked whether inclusion of the FLAG epitope in the fourth extracellular loop of the cystic fibrosis transmembrane conductance regulator (M2-901/CFTR), which permits detection of cell surface expression, affected CFTR's biophysical properties or channel regulation by kinases, phosphatases, and nucleotides. Channel activity of M2-901/CFTR was evaluated in numerous cell types and expression systems to characterize its gating and regulation. Our results show that M2-901/CFTR required adenosine 3',5'-cyclic monophosphate-dependent protein kinase phosphorylation to initiate channel activity. Subsequently, ATP alone was sufficient to support channel gating, and ADP inhibited channel opening. Current fluctuation analysis indicated that the nucleotide-dependent gating rates were indistinguishable from those of wild-type (wt) cystic fibrosis transmembrane conductance regulator (CFTR). Channel conductance in symmetric Cl- (11.2 pS), anion permeability ratio (1.66), and block by gluconate indicate that the anion conduction pathway is indistinguishable from wtCFTR. Sulfonylureas (glibenclamide and LY-295501) inhibited M2-901/ CFTR channel activity by an identical mechanism to that described for wtCFTR. Finally, CFTR-dependent insertion a...Continue Reading
References
Nov 5, 1992·Nature·G NagelD C Gadsby
Oct 1, 1992·The Journal of General Physiology·D N Sheppard, M J Welsh
Apr 24, 1992·Science·N A BradburyK L Kirk
Dec 15, 1992·Biochimica Et Biophysica Acta·S J Ashcroft, F M Ashcroft
Feb 14, 1992·Analytical Biochemistry·S P Brooks, K B Storey
Nov 16, 1990·Cell·S H ChengA E Smith
Jul 12, 1991·Science·M P AndersonM J Welsh
Aug 1, 1991·The Journal of Clinical Investigation·C R MarinoJ A Cohn
Aug 15, 1991·Nature·J A TabcharaniJ W Hanrahan
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·I CrawfordC F Higgins
Dec 19, 1991·Nature·W DalemansM Lazdunski
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Nov 24, 1995·The Journal of Biological Chemistry·J XieP B Davis
Mar 25, 1994·Cell·D N SheppardM J Welsh
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·J J BowdenD M McDonald
Sep 1, 1994·Neuron·S McDonoughN A McCarty
Jul 1, 1994·The Journal of General Physiology·C J VenglarikR J Bridges
Mar 1, 1995·The Journal of General Physiology·B D SchultzR A Frizzell
Mar 1, 1995·Pflügers Archiv : European journal of physiology·A RabeE Frömter
Jul 2, 1993·Cell·M J Welsh, A E Smith
Sep 1, 1993·The American Journal of Physiology·A P MorrisR A Frizzell
Dec 1, 1995·The American Journal of Physiology·M HowardR A Frizzell
May 1, 1996·The Journal of Membrane Biology·B D SchultzR A Frizzell
Jun 1, 1996·Kidney International·M HowardR A Frizzell
Jun 1, 1996·Biophysical Journal·C J VenglarikR J Bridges
Aug 1, 1996·The American Journal of Physiology·P Linsdell, J W Hanrahan
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·D FirsovB C Rossier
Dec 1, 1996·The American Journal of Physiology·A TakahashiR A Frizzell
Mar 1, 1997·The Journal of General Physiology·M Cheung, M H Akabas
Citations
Jan 30, 2002·Journal of Dairy Science·C R SchmidtB D Schultz
Aug 27, 2003·The Journal of General Physiology·Claudia BassoDavid C Gadsby
May 21, 2004·American Journal of Physiology. Cell Physiology·James R BroughmanBruce D Schultz
Sep 13, 2007·Journal of Cellular Physiology·Robert A Maue
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jiraporn OusingsawatKarl Kunzelmann
Jan 13, 2015·Molecular Biotechnology·Ellen HildebrandtJohn C Kappes
Jul 8, 2017·BioMed Research International·Elena KrachmarovaGenoveva Nacheva
Dec 24, 2018·Pharmacological Reviews·Yasunobu OkadaRavshan Z Sabirov
Sep 26, 2000·American Journal of Physiology. Cell Physiology·G A GibsonO A Weisz
Jul 17, 1999·The American Journal of Physiology·K W PetersR A Frizzell
Aug 15, 2001·American Journal of Physiology. Renal Physiology·R L SedlacekB D Schultz
Jan 18, 2017·British Journal of Pharmacology·Emily LangronPaola Vergani
Jul 27, 2000·American Journal of Physiology. Cell Physiology·M HowardO A Weisz
Jan 29, 1999·Physiological Reviews·D N Sheppard, M J Welsh
Feb 8, 2006·Neuroreport·Zhi-Ling Guo, John C Longhurst
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A W WolkoffB F Scharschmidt
Mar 19, 2013·The Journal of Biological Chemistry·Aixia RenAnjaparavanda P Naren
Aug 2, 2013·American Journal of Physiology. Cell Physiology·Sheng YiBruce D Schultz
Feb 3, 1999·Annual Review of Genetics·J W Jarvik, C A Telmer
Oct 29, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·E K O'DonnellB D Schultz
Jan 29, 1999·Physiological Reviews·B D SchultzR J Bridges
Apr 25, 2000·Molecular Cell Biology Research Communications : MCBRC·D M LarsonE C Beyer
Jun 13, 2001·Biochemical and Biophysical Research Communications·E J Kamsteeg, P M Deen
Sep 23, 2000·European Journal of Cell Biology·B KleizenH R de Jonge
May 23, 2006·Biophysical Journal·Ian R BatesJohn W Hanrahan