ABCMdb

PMID: 9530164

Berger HA, Travis SM, Welsh MJ
Fluoride stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.
Am J Physiol. 1998 Mar;274(3 Pt 1):L305-12., [PubMed]

Sentences

No. Mutations Sentence Comment

127 ABCC7 p.Ser660Ala Effect of F2 on CFTRDR-S660A current. Because CFTR requires phosphorylation for activation and because F2 is known to inhibit several protein phosphatases (34), we asked whether F2 might stimulate CFTR activity by inhibiting a phosphatase. Login to comment 128 ABCC7 p.Ser660Ala To test this possibility, we studied a CFTR variant (CFTRDR-S660A) in which part of the R domain (amino acids 708-835) is deleted and a remaining phosphorylation site (serine 660) is mutated to alanine (30). Login to comment 130 ABCC7 p.Ser660Ala Figure 5 shows that addition of F2 increased the current in CFTRDR-S660A (n 5 3), suggesting that F2 did not stimulate the channel by inhibiting a phosphatase. Login to comment 134 ABCC7 p.Ser660Ala Effect of Fon CFTR⌬R-S660A current. Because CFTR requires phosphorylation for activation and because Fis known to inhibit several protein phosphatases (34), we asked whether F- might stimulate CFTR activity by inhibiting a phosphatase. Login to comment 135 ABCC7 p.Ser660Ala To test this possibility, we studied a CFTR variant (CFTR⌬R-S660A) in which part of the R domain (amino acids 708-835) is deleted and a remaining phosphorylation site (serine 660) is mutated to alanine (30). Login to comment 137 ABCC7 p.Ser660Ala Figure 5 shows that addition of F- increased the current in CFTR⌬R-S660A (n ϭ 3), suggesting that F- did not stimulate the channel by inhibiting a phosphatase. Login to comment 150 ABCC7 p.Ser660Ala Effect of F2 on Cl2 current in CFTRDR-S660A. Login to comment 151 ABCC7 p.Ser660Ala Data show time course of current in an excised, inside-out membrane patch from NIH/3T3 cells expressing CFTRDR-S660A. Login to comment 157 ABCC7 p.Ser660Ala Effect of Fon Cl- current in CFTR⌬R-S660A. Login to comment 158 ABCC7 p.Ser660Ala Data show time course of current in an excised, inside-out membrane patch from NIH/3T3 cells expressing CFTR⌬R-S660A. Login to comment 171 ABCC7 p.Lys1250Met We found that F2 stimulates CFTR-K1250M channels to a greater extent than wild-type CFTR (Fig. 8). Login to comment 175 ABCC7 p.Ser660Ala The effect of F2 was likely independent of phosphatase inhibition, since F2 increased current in CFTRDR-S660A. Login to comment 178 ABCC7 p.Lys1250Met We found that F- stimulates CFTR-K1250M channels to a greater extent than wild-type CFTR (Fig. 8). Login to comment 182 ABCC7 p.Ser660Ala The effect of F- was likely independent of phosphatase inhibition, since F- increased current in CFTR⌬R-S660A. Login to comment 193 ABCC7 p.Ser660Ala It seemed unlikely that F2 stimulated through an interaction with the R domain because F2 stimulated CFTRDR-S660A. Login to comment 201 ABCC7 p.Ser660Ala It seemed unlikely that F- stimu- lated through an interaction with the R domain because F- stimulated CFTR⌬R-S660A. Login to comment 213 ABCC7 p.Lys1250Met ABCC7 p.Lys1250Met More strikingly, PPi stimulated less current in K1250M-CFTR than in wild-type CFTR (14), whereas F2 stimulated more current in K1250M-CFTR than in wild-type CFTR. Therefore, there are distinct differences between the effects of F2 and PPi. Login to comment 221 ABCC7 p.Lys1250Met ABCC7 p.Lys1250Met More strikingly, PPi stimulated less current in K1250M-CFTR than in wild-type CFTR (14), whereas F- stimulated more current in K1250M-CFTR than in wild-type CFTR. Therefore, there are distinct differences between the effects of F- and PPi. Login to comment 222 ABCC7 p.Lys464Ala ABCC7 p.Lys1250Met Effect of increasing F2 concentration on current in wild-type CFTR, CFTR-K464A, and CFTR-K1250M. Login to comment 225 ABCC7 p.Lys464Ala *P , 0.005 compared with wild-type CFTR and *P , 0.026 compared with CFTR-K464A. Login to comment 230 ABCC7 p.Lys464Ala ABCC7 p.Lys1250Met Effect of increasing F- concentration on current in wild-type CFTR, CFTR-K464A, and CFTR-K1250M. Login to comment 233 ABCC7 p.Lys464Ala *P Ͻ 0.005 compared with wild-type CFTR and *P Ͻ 0.026 compared with CFTR-K464A. Login to comment