ABCMdb

ABCC7 p.Ser511Ala

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

94 Generation of the S511A Mutant in the NBD1 Region of CFTR-The cftr gene-specific primers, forward, 5Ј-tcatctttggtgttgcctat- gatgaatat-3Ј, and reverse, 5Ј-atattcatcataggcaacaccaaagatga-3Ј, were used to introduce a Ser to Ala point mutation at the 511 site in the CFTR NBD1 region using PfuTurbo DNA polymerase in a PCR-based method (Quickchange SDM kit, Invitrogen). Login to 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
189 Phosphorylation assays using NBD1/ NBD1-S511A protein demonstrated that PKA-dependent phosphorylation remained intact. Login to comment
190 In contrast, CK2 failed to phosphorylate the S511A mutant (Fig. 5D, open columns). Login to comment
211 These results suggest that neither ⌬F508-NBD1 nor S511A-NBD1 domains interact with CK2 in vitro; we therefore investigated whether this defect is mirrored in full-length CFTR. Login to comment
212 Wild-type, but Not ⌬F508 or S511A CFTR, Induces CK2 Membrane Localization-Having shown that CK2 membrane localization is dependent on the presence of wild-type CFTR in bronchial cell lines, we investigated whether this phenomenon could be reproduced by expression of CFTR in a CFTR-naive cell line. 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
228 S511D (ϮF508) and S511A decreased the Po of CFTR 3-fold, without altering current flow through individual chan- FIGURE 5. Login to comment
237 D, CK2-dependent but not PKA-dependent phosphorylation is abolished in S511A-NBD1; CK2 and PKA phos- phorylatewild-typeNBD1additivelyatdistinctsites,andtheirrespectiveinhibitorsarespecific(nϭ3Ϯrange). 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
268 CK2 association with CFTR is abrogated by ⌬F508 or S511A mutation; CK2 phosphorylates CFTR at Ser-511 in vivo. 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
248 Values are means + SEM (n = 6, except S511A where n = 4). Login to comment
255 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

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

No. Sentence Comment

5 Fragments change their size/pattern again post-mutation at sites involved in CFTR`s in vitro interaction with the pleiotropic protein kinase CK2 (S511A in NBD1). Login to 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
197 S511A-CFTR and its cognate NBD2 The diffuse 80 kDa NBD2 and the C-terminal-bearing fragment so characteristic of the wt-CFTR fingerprint is now grossly attenuated (Figure 7C, compare lanes 2 and 5). Login to comment
199 First, the fragment bearing NBD2 and the C-terminus of CFTR may be more easily degraded when the N-terminal 110 kDa (NDB1/N-terminal) fragment (Figures 7A and 7B) is generated by the S511A mutation. Login to comment
200 Secondly, the epitope of NBD2 recognized by this monoclonal antibody (WPSGGQMT) may be masked after S511A mutation by some post-translational event. Login to comment
201 Thirdly, the CFTR fracture point induced by this S511A mutant lies near this region as opposed to the R-domain region seen with wt-CFTR in the Figures above. Login to comment
202 S511A-CFTR and its cognate NBD1 Consistent with the idea of an altered fracture point when S511A-CFTR is present, a new faint ~100-110 kDa band appears. 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
211 Thus it is probable that the S511A mutation creates a band at 100-110 kDa-bearing NBD1 and the N-terminus, but we cannot be sure about the relationship between this band and the relative amounts of the Q1-Q4 NBD1-bearing fragments. Login to comment
214 The combined S511 site mutant data suggest the existence of a new S511A-dependent CFTR cleavage whose generation is either dependent on the non-availability of the expected wt hydroxy group on S511 or is induced by a structural change after substitution with alanine (but not the negatively charged aspartate). 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
223 Only F508delCFTR and S511A CFTR generated a new CFTR band at about 110 kDa. 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