ABCMdb

PMID: 19910675

Treharne KJ, Xu Z, Chen JH, Best OG, Cassidy DM, Gruenert DC, Hegyi P, Gray MA, Sheppard DN, Kunzelmann K, Mehta A
Inhibition of protein kinase CK2 closes the CFTR Cl channel, but has no effect on the cystic fibrosis mutant deltaF508-CFTR.
Cell Physiol Biochem. 2009;24(5-6):347-60. Epub 2009 Nov 4., [PubMed]

Sentences

No. Mutations Sentence Comment

216 ABCC7 p.Ser511Ala ABCC7 p.Ser511Asp Figure 7a demonstrates that mutation of S511 in wild-type CFTR is without effect on the single-channel activity of CFTR; neither the i nor the Po of S511A- and S511D-CFTR differed from those of wild-type CFTR when measured in excised inside-out membrane patches from BHK cells stably expressing CFTR constructs. Login to comment 217 ABCC7 p.Ser511Asp By contrast, the Po of ΔF508-CFTR was attenuated sharply compared with that of wild-type CFTR and no channel activity was detected in BHK cells expressing the construct ΔF508-S511D-CFTR, when BHK cells were cultured at 37 °C (Fig. 7a). Login to comment 229 ABCC7 p.Ser511Asp Figure 7b demonstrates that TBB (1 µM) was without significant effect on cAMP-stimulated CFTR Cl- currents in oocytes expressing S511D-CFTR. Login to comment 231 ABCC7 p.Ser511Asp ABCC7 p.Ser511Asp Processing of ΔF508-S511D-CFTR is more efficient in oocytes and thus ΔF508-S511D-CFTR generated a cAMP-stimulated CFTR Cl- current that was also unaffected by TBB (1 µM). Login to comment 248 ABCC7 p.Ser511Ala Values are means + SEM (n = 6, except S511A where n = 4). Login to comment 250 ABCC7 p.Ser511Asp No channel activity was detected in 8 membrane patches excised from BHK cells expressing ΔF508-S511D grown at 37 ºC. Login to comment 251 ABCC7 p.Ser511Asp (b) TBB insensitivity of S511D-CFTR. Login to comment 252 ABCC7 p.Ser511Asp S551D and S511D-ΔF508-CFTR constructs were expressed in Xenopus oocytes and tested for TBB (1 µM) sensitivity in the presence of cAMP agonists. Login to comment 255 ABCC7 p.Ser511Ala It was not possible to study the construct S511A-CFTR in Xenopus oocytes because for unknown reasons oocytes expressing this construct all died immediately after microelectrode impalement. Login to comment 284 ABCC7 p.Ser511Asp In particular, the data shown in Figure 7 demonstrate that S511D-CFTR is insensitive to TBB inhibition even though S511 is not a CK2 target. Login to comment 345 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp J Biol Chem 2000;275:36632-36636. 35 Cai Z, Taddei A, Sheppard DN: Differential sensitivity of the cystic fibrosis (CF)-associated mutants G551D and G1349D to potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel. Login to comment