ABCC1 p.Arg1249Ala
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No.
Sentence
Comment
223
For example, the R1249A mutant of MRP1 has been described as having altered substrate specificity.
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ABCC1 p.Arg1249Ala 19406100:223:17
status: NEW
PMID: 12450376
[PubMed]
Ren XQ et al: "A positively charged amino acid proximal to the C-terminus of TM17 of MRP1 is indispensable for GSH-dependent binding of substrates and for transport of LTC4."
No.
Sentence
Comment
9
Mutation of this arginine to alanine (R1249A) resulted in a decreased level of GSH-dependent azido AG-A photolabeling of MRP1.
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ABCC1 p.Arg1249Ala 12450376:9:38
status: NEW72 MRP1 constructs encoding R1222M and R1249A were generated in a PCR using the forward primers 5'-CATG- CACAGCCTCAGTGCTG-3' and 5'-GCGATGTCATCT- GAAATGGAAACC-3', respectively (bold denotes mismatched bases encoding the mutations).
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ABCC1 p.Arg1249Ala 12450376:72:36
status: NEW168 To investigate the role of charged amino acids in GSH-dependent photolabeling of azido AG-A to MRP1, we replaced the arginine at position 1249 which is proximal to the C-terminus of TM17 of MRP1 with Ala (R1249A).
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ABCC1 p.Arg1249Ala 12450376:168:205
status: NEW169 Arginine at position 1222 in the azido AG-A-photolabeled MRP11-1222 fragment was replaced with Met, and the functions of MRP1 R1222M were compared with those of MRP1 R1249A.
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ABCC1 p.Arg1249Ala 12450376:169:166
status: NEW190 Figure 6A shows that the expression level of MRP1 R1222M was comparable to that of wild-type MRP1, whereas the expression level of MRP1 R1249A was higher than that of wild-type MRP1.
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ABCC1 p.Arg1249Ala 12450376:190:136
status: NEW193 However, the transport activities of MRP1 R1249A were considerably reduced, suggesting that Arg1249 was important for the LTC4 transporting activity of MRP1.
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ABCC1 p.Arg1249Ala 12450376:193:42
status: NEW196 The level of photolabeling of MRP1 R1249A with [125 I]azido AG-A was increased only 1.6-fold in the presence of 10 mM GSH compared to a 10-fold increase observed with wild-type MRP1.
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ABCC1 p.Arg1249Ala 12450376:196:35
status: NEW198 To test the ability of MRP1 R1249A to confer drug resistance, wild-type MRP1 and the MRP1 R1249A mutant cDNAs were cloned into the mammalian expression vector pCIneo and transfected into pig kidney LLC-PK1 cells.
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ABCC1 p.Arg1249Ala 12450376:198:28
status: NEWX
ABCC1 p.Arg1249Ala 12450376:198:90
status: NEW202 Transfection of the pCIneo empty vector or the MRP1 R1249A mutant resulted in no VCR resistant clones.
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ABCC1 p.Arg1249Ala 12450376:202:52
status: NEW203 However, limited dilution of G418 resistant mass populations transfected with the MRP1 R1249A mutant in the medium without VCR resulted in several clones expressing MRP1 R1249A (Figure 7A).
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ABCC1 p.Arg1249Ala 12450376:203:87
status: NEWX
ABCC1 p.Arg1249Ala 12450376:203:170
status: NEW205 As shown in Figure 7B, the MRP1 R1249A mutant impaired the ability to confer resistance to VCR on LLC-PK1 cells.
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ABCC1 p.Arg1249Ala 12450376:205:32
status: NEW206 To determine if the inability of the R1249A mutant to confer drug resistance might be due to an inability of the mutant protein to reach the cell membrane, we assessed the cellular localization of MRP1 R1249A by immunofluorescence using MRPm6 mAb. As shown in Figure 7C, the MRP1 R1249A mutant was localized to the plasma membrane in a manner similar to that of wild-type MRP1.
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ABCC1 p.Arg1249Ala 12450376:206:37
status: NEWX
ABCC1 p.Arg1249Ala 12450376:206:202
status: NEWX
ABCC1 p.Arg1249Ala 12450376:206:280
status: NEW207 Thus, the inability of R1249A to confer drug resistance was not due to impaired trafficking of the protein.
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ABCC1 p.Arg1249Ala 12450376:207:23
status: NEW225 Membrane vesicles (25 µg of protein) expressing MRP1 R1222M or MRP1 R1249A as indicated were incubated with 1.37 nM [3H]LTC4 at 37 °C in 50 µL of transport buffer as described in the legend of Figure 3 in the presence or absence of 4 mM ATP at the indicated periods.
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ABCC1 p.Arg1249Ala 12450376:225:73
status: NEW259 Mutation of this FIGURE 7: Effect of the R1249A mutation in MRP1 on drug resistance in LLC-PK1 cells.
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ABCC1 p.Arg1249Ala 12450376:259:41
status: NEW260 (A) Expression of MRP1 and the MRP1 R1249A mutant in LLC-PK1 cells.
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ABCC1 p.Arg1249Ala 12450376:260:36
status: NEW261 Crude membranes (50 µg of protein) prepared from LLC-PK1 cells transfected with an expression vector encoding MRP1 or MRP1 R1249A, or with a control empty vector (pCIneo), were analyzed on 7.5% SDS-PAGE.
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ABCC1 p.Arg1249Ala 12450376:261:128
status: NEW264 LLC-PK1 cells expressing MRP1 (b) or MRP1 R1249A (0), or the cells transfected with an empty vector [pCIneo (O)], were exposed to the indicated concentrations of VCR, and the survival rates were determined.
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ABCC1 p.Arg1249Ala 12450376:264:42
status: NEW268 Indirect immunofluorescent staining of MRP1 and MRP1 R1249A expressed in LLC-PK1 cells was carried out with the MRPm6 mAb and an FITC-conjugated secondary antibody.
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ABCC1 p.Arg1249Ala 12450376:268:53
status: NEW271 arginine 1249 to alanine almost completely impaired the LTC4 transport activity of MRP1 and abrogated the ability of MRP1 to confer VCR resistance.
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ABCC1 p.Arg1249Ala 12450376:271:0
status: NEW273 The inability of R1249A to confer VCR resistance was not due to alterations in MRP1 trafficking since the mutant MRP1 was still localized to the plasma membrane.
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ABCC1 p.Arg1249Ala 12450376:273:17
status: NEW
PMID: 14965249
[PubMed]
Haimeur A et al: "The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation."
No.
Sentence
Comment
276
Additional mutations of charged residues that lead to defective MRP1 transport activity (or altered drug interactions) have been described (e.g. TM16 Arg1202Gly and TM17 Arg1249Ala) but because only one or two substrates were tested in these studies, it is not possible to know whether the altered activity is relatively substrate selective or more global in nature [167, 168].
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ABCC1 p.Arg1249Ala 14965249:276:170
status: NEW
PMID: 15208328
[PubMed]
Situ D et al: "Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter."
No.
Sentence
Comment
229
Unlike Arg1202 and Glu1204 , substitution of Arg1197 and Arg1249 with oppositely charged residues did not adversely affect expression of MRP1 but instead caused a substantial reduction in transport activity. Our observations with respect to the R1249D mutant are consistent with those of Ren et al. (19) who reported that Ala substitution of Arg1249 impaired MRP1-mediated LTC4 transport and reduced vincristine resistance.
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ABCC1 p.Arg1249Ala 15208328:229:322
status: NEW
PMID: 15579473
[PubMed]
Ren XQ et al: "GSH inhibits trypsinization of the C-terminal half of human MRP1."
No.
Sentence
Comment
219
We had previously mutated Arg1249 to Ala (32) and therefore tested this mutant for the generation of the C2 fragment following trypsin digestion.
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ABCC1 p.Arg1249Ala 15579473:219:26
status: NEW
PMID: 18612080
[PubMed]
El-Sheikh AA et al: "Functional role of arginine 375 in transmembrane helix 6 of multidrug resistance protein 4 (MRP4/ABCC4)."
No.
Sentence
Comment
230
Moreover, alanine substitution of Arg1249 in MRP1 (also corresponding to R998A) impaired MRP1-mediated LTC4 transport and reduced vincristine resistance (Ren et al., 2002).
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ABCC1 p.Arg1249Ala 18612080:230:10
status: NEW