ABCMdb

ABCC7 p.Ser511Asp

None has been submitted yet.

Publications

PMID: 17289674 [PubMed] Treharne KJ et al: "Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the deltaF508 mutation: F508 deletion disrupts a kinase-binding site."

No. Sentence Comment

102 Co-immunoprecipitation of CK2 with CFTR Mutants-BHK cells were transfected with vectors encoding wild-type, ⌬F508, S511A, or S511D CFTR. Login to comment
216 No CK2 protein was found associated with S511A or ⌬F508 mutant CFTR, whereas wild-type, S511D, and the ⌬F508-S511D double mutant CFTR all bound CK2 (Fig. 6A). Login to comment
218 CK2 activity was present in wild-type, S511D, and ⌬F508-S511D-CFTR-transfected membranes but was absent from those of S511A and ⌬F508 (Fig. 6B). Login to comment
219 Thus, the S511D mutation rescues the CFTR-CK2 association abolished by ⌬F508. Login to comment
221 Hep-G2 (human liver) cells were transfected with either wild-type or S511D CFTR (eliminating the putative CK2 target serine at Ser-511) using vectors encoding either NBD1 alone or full-length CFTR. Login to comment
224 In cells expressing full-length CFTR, either adding TBB or transfecting S511D CFTR reduces the phosphoserine content; however, the effect of CK2 inhibition is more pronounced than Ser-511 mutation (Fig. 6C, right histogram). Login to comment
228 S511D (ϮF508) and S511A decreased the Po of CFTR 3-fold, without altering current flow through individual chan- FIGURE 5. Login to comment
242 TBB failed to inhibit the cAMP-dependent chloride currents generated by S511D CFTR or the doubly mutated ⌬F508-S511D CFTR (Fig. 7B, compare with wild type, Fig. 3A), even though these mutants both bind CK2. Login to comment
258 The Po observed in S511A/S511D was similar to that of ⌬F508 CFTR when it is induced to traffic to the membrane by a low temperature correction. Login to comment
261 Thus we find that S511A and ⌬F508 share an inability to bind CK2, but S511D restores CK2 binding with or without F508. Login to comment
267 Interestingly, unlike ⌬F508-CFTR (40), neither S511D nor ⌬F508-S511D-CFTR required incubation at low temperature to detect channel activity at the plasma membrane in CHO cells FIGURE 6. Login to comment

PMID: 19910675 [PubMed] Treharne KJ et al: "Inhibition of protein kinase CK2 closes the CFTR Cl channel, but has no effect on the cystic fibrosis mutant deltaF508-CFTR."

No. Sentence Comment

216 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 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 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 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
250 No channel activity was detected in 8 membrane patches excised from BHK cells expressing ΔF508-S511D grown at 37 ºC. Login to comment
251 (b) TBB insensitivity of S511D-CFTR. Login to comment
252 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
284 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

PMID: 23067305 [PubMed] Tosoni K et al: "CFTR mutations altering CFTR fragmentation."

No. Sentence Comment

6 The F508del and S511A mutations generate different fragmentation fingerprints that are each unlike the wild-type; yet, both mutants generate new N-terminal-bearing CFTR fragments that are not observed with other CK2-related mutations (S511D, S422A/D and T1471A/D). Login to comment
44 Cell culture, lysis, protein solubilization and Western blotting The cell culture methods to create the stable CFTR-expressing cell lines (WT, F, WT S422A, WT S422D, WT S511A, WT S511D, WT T1471A and WT T1471D) and their culture protocols have been described recently [25]. Login to comment
204 Note the N-terminal- and NBD1- (but not NBD2) bearing ~120 kDa fragment seen after S511A (but not S511D) mutation in lanes 5 and 6 in (A) and (B), but not in (C) and (D), the latter probing the C-terminus. Login to comment
212 S511D-CFTR and NBD1 and NBD2 This phosphomimic fingerprint is similar to the wt in fragmentation pattern and no 110 kDa band appears, even after overexposure (Figure 7, lanes 6 and results not shown). Login to comment
220 In summary, the two S511A/S511D and T1471A/T1471D pairs manifested very different CFTR cleavage patterns and abundance of full-length CFTR when present on a wt background. Login to comment
233 It is also unlikely that CK2-relevant CFTR mutants such as S511A- and S511D-CFTR generate an ER-trapped unfolded CFTR, as they have wt patterns of maturation and turnover during pulse-chase experiments in the same cell line [25]; yet, they manifest very different fragmentation. Login to comment