ABCMdb

ABCC7 p.Lys978Ser

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Publications

PMID: 20133716 [PubMed] Wang W et al: "ATP-independent CFTR channel gating and allosteric modulation by phosphorylation."

No. Sentence Comment

113 Fig. 3 shows that the K978C and K978S mutations markedly increased the macroscopic currents mediated by G551D-CFTR (the most common CF regulation mutant) and by Δ1198-CFTR (a deletion construct that lacks NBD2 and the carboxy terminal tail). Login to comment
117 Introducing the K978C or K978S mutation strongly enhanced the basal activities of G551D-CFTR and Δ1198-CFTR Fig. 2. Login to comment
130 The relative degree of curcumin activation of the K978S/C combination mutants was much lower than for the original G551D and Δ1198-CFTR constructs (Fig. 3E), consistent with the substantial elevation of basal channel activity by these substitutions. Login to comment
138 (C-E) High control currents for G551D and Δ1198-CFTR channels containing K978C or K978S mutations. Login to comment
146 The currents mediated by K978S/G551D and K978C/G551D were statistically greater than the G551D currents (P < 0.05, unpaired t test). Login to comment

PMID: 17582383 [PubMed] Melin P et al: "CFTR inhibition by glibenclamide requires a positive charge in cytoplasmic loop three."

No. Sentence Comment

2 Charge-neutralizing mutations K978A, K978Q, K978S abolished the inhibition of forskolin-activated CFTR chloride current by glibenclamide but not by CFTRinh-172. Login to comment
78 Effect of K978S mutation on the whole cell EGFP-CFTR chloride currents. Login to comment
79 Representative traces of global currents recorded on HEK-293 transfected with EGFP-CFTR channels wild-type (left) and charge neutralizing mutant K978S (right) are shown in presence of Fsk 10 bc;M (A), after perfusion of glibenclamide 100 bc;M (B), and sub-sequential addition of CFTRinh-172 10 bc;M (C). Login to comment
80 (D) Corresponding current-voltage relationships normalized by cell capacitance (n=6 for wt, n=10 for K978S). Login to comment
81 K978S compared to CFTR-wt. Login to comment
84 Similar effects in the presence of Fsk were recorded with cells expressing K978A, K978Q, K978R and K978S mutants CFTR. Login to comment
85 Representative chloride currents recorded with K978S are shown in Fig. 2A (right). Login to comment
87 Interestingly, perfusion of glibenclamide did not induce inhibition of forskolin-activated chloride currents in EGFP-CFTR-K978S expressing cells (Fig. 2B right). Login to comment
88 The difference between the two I/V curves in the presence of Fsk versus Fsk+Glib, at all voltages for K978S channels, was not statistically different (PN0.05) using analysis of variance followed by a Bonferroni post hoc test (Fig. 2D right). Login to comment
92 In contrast, K978S activity, after glibenclamide application, was fully inhibited by CFTRinh-172 (Fig. 3A, right). Login to comment
93 From continuous whole cell recordings with voltage steps between -40 mV and +40 mV, we estimated that full inhibition of CFTR-wt current by glibenclamide was achieved in ~250 s (Fig. 3B left) whereas K978S activity remained remarkably stable as long as the sulfonylurea was present (Fig. 3B right). Login to comment
94 The inhibition by CFTRinh-172 of CFTR-K978S was, on the contrary, almost immediate and very rapid as illustrated at the end of the recording, Fig. 3B (right). Login to comment
95 Thus, the charge neutralizing mutant K978S is resistant to glibenclamide block, but remains sensitive to the blocker CFTRinh-172. Login to comment
98 Fig. 4A presents the ratio Iglib/Ifsk, recorded at -100 mV, with 100 bc;M glibenclamide, for K978A, K978Q, K978R, K978S channels compared to CFTR-wt. Login to comment
101 However, for K978S channels, the ratio at this voltage was significantly (Pb0.001) increased to 0.81&#b1;0.04 (n=4). Login to comment
104 (A) Summary of mean current densities (pA/pF), recorded at -100 mV and +40 mV, in various conditions (indicated on graph) for HEK cells transfected with EGFP-CFTR-wt (left) or EGFP-CFTR-K978S (right). Login to comment
105 Data are mean&#b1;S.E.M. of n experiments (n=7 for wt, n=10 for K978S). Login to comment
107 Note that EGFP-CFTR-K978S channels were inhibited by CFTRinh-172 but not by glibenclamide. Login to comment
119 For K978S channels, refractory to glibenclamide, the experimental reversal potentials were -43&#b1;1.5 mV (n=4) for bromide, -42.5&#b1; 1.5 mV (n=4) for chloride, and -29&#b1;5 mV (n=3) for iodide. Login to comment
138 This was the case for the mutations that neutralized the charge of the side chain of the residue 978 (K978A, K978Q, K978S). Login to comment

PMID: 23620589 [PubMed] Okeyo G et al: "Converting nonhydrolyzable nucleotides to strong cystic fibrosis transmembrane conductance regulator (CFTR) agonists by gain of function (GOF) mutations."

No. Sentence Comment

162 In an earlier study we found that GOF mutations at residue 978 (K978C or K978S) promoted a substantial ATP-independent activity for the G551D mutant that could be augmented further by curcumin (13). Login to comment
259 In this regard, the substitutions at position Lys-978 that had the strongest GOF effects (K978C, K978S, and K978P; Ref. 13) also are predicted to have the greatest disruptive effects on the presumed helical structure of cytosolic loop3 and TM9 based on secondary structure predictions (results not shown). Login to comment