ABCC2 p.Ser1542Glu
| Predicted by SNAP2: | A: N (87%), C: N (66%), D: N (82%), E: N (87%), F: N (66%), G: N (82%), H: N (93%), I: N (78%), K: N (87%), L: N (72%), M: N (72%), N: N (93%), P: N (66%), Q: N (82%), R: N (82%), T: N (93%), V: N (78%), W: D (53%), Y: N (66%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: N, Y: N, |
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[hide] C-terminal phosphorylation of MRP2 modulates its i... Biochem Biophys Res Commun. 2003 Mar 14;302(3):454-61. Hegedus T, Sessler T, Scott R, Thelin W, Bakos E, Varadi A, Szabo K, Homolya L, Milgram SL, Sarkadi B
C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins.
Biochem Biophys Res Commun. 2003 Mar 14;302(3):454-61., [PMID:12615054]
Abstract [show]
MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in the targeting of MRP2, we found a potential PKC phosphorylation site (Ser(1542)). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, beta2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas beta2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2.
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No. Sentence Comment
38 The binding of EBP50 and IKEPP was studied to mutant MRP2 variants (S1542A and S1542E), mimicking the non-phosphorylated and the phosphorylated serine, respectively.
X
ABCC2 p.Ser1542Glu 12615054:38:79
status: NEW104 In order to investigate the role of this residue in PDZ interactions, the serine was replaced either by alanine (MRP2 S1542A) or by glutamic acid (MRP2 S1542E).
X
ABCC2 p.Ser1542Glu 12615054:104:152
status: NEW105 MRP2 S1542A mimicked the dephosphorylated, while MRP2 S1542E the phosphorylated states of the PDZ binding motif.
X
ABCC2 p.Ser1542Glu 12615054:105:54
status: NEW107 The MRP2 S1542E mutant interacted with EBP50 much stronger than the wild type MRP2, whereas the MRP2 S1542A variant showed less EBP50 binding compared to the wild type MRP2.
X
ABCC2 p.Ser1542Glu 12615054:107:9
status: NEWX
ABCC2 p.Ser1542Glu 12615054:107:54
status: NEW109 The autoradiogram shown in Fig. 3B reveals that the MRP2 S1542E mutant bound IKEPP much more efficiently than the wild type MRP2.
X
ABCC2 p.Ser1542Glu 12615054:109:9
status: NEWX
ABCC2 p.Ser1542Glu 12615054:109:57
status: NEW116 We found that the interaction of IKEPP with the MRP2 S1542E mutant was stronger in the full concentration range, as Table 1 Summary of the overlay experiments PDZ/ABC proteins MRP2 CFTR ABCA1 PDZK1 +* +* ) IKEPP + + ) EBP50 + + ) E3KARP ) + ) SAP-97 ) ) ) b2-syntrophin ) ) + Interacting pairs of ABC and PDZ proteins are labeled as ''+``, whereas '')`` represents the pairs which exhibited no binding in our overlay experiments.
X
ABCC2 p.Ser1542Glu 12615054:116:53
status: NEW121 Similar experiments with EBP50 showed a preferential binding of this PDZ protein to MRP2 S1542E at various EBP50 concentrations (data not shown).
X
ABCC2 p.Ser1542Glu 12615054:121:89
status: NEW141 Wild type (WT), mutants mimicking the phosphorylated (S1542E) and dephosphorylated (S1542A) states of PDZ binding motif, and a variant containing glycines in place of the last four, C-terminal amino acids (4G), were studied.
X
ABCC2 p.Ser1542Glu 12615054:141:54
status: NEW162 The binding of the phosphorylation mimicking MRP2 S1542E mutant and the phosphorylated C-terminal peptide to EBP50 changed in our experiments.
X
ABCC2 p.Ser1542Glu 12615054:162:50
status: NEW39 The binding of EBP50 and IKEPP was studied to mutant MRP2 variants (S1542A and S1542E), mimicking the non-phosphorylated and the phosphorylated serine, respectively.
X
ABCC2 p.Ser1542Glu 12615054:39:79
status: NEW106 In order to investigate the role of this residue in PDZ interactions, the serine was replaced either by alanine (MRP2 S1542A) or by glutamic acid (MRP2 S1542E).
X
ABCC2 p.Ser1542Glu 12615054:106:152
status: NEW111 The autoradiogram shown in Fig. 3B reveals that the MRP2 S1542E mutant bound IKEPP much more efficiently than the wild type MRP2.
X
ABCC2 p.Ser1542Glu 12615054:111:57
status: NEW118 We found that the interaction of IKEPP with the MRP2 S1542E mutant was stronger in the full concentration range, as Table 1 Summary of the overlay experiments PDZ/ABC proteins MRP2 CFTR ABCA1 PDZK1 +* +* ) IKEPP + + ) EBP50 + + ) E3KARP ) + ) SAP-97 ) ) ) b2-syntrophin ) ) + Interacting pairs of ABC and PDZ proteins are labeled as ''+``, whereas '')`` represents the pairs which exhibited no binding in our overlay experiments.
X
ABCC2 p.Ser1542Glu 12615054:118:53
status: NEW123 Similar experiments with EBP50 showed a preferential binding of this PDZ protein to MRP2 S1542E at various EBP50 concentrations (data not shown).
X
ABCC2 p.Ser1542Glu 12615054:123:89
status: NEW143 Wild type (WT), mutants mimicking the phosphorylated (S1542E) and dephosphorylated (S1542A) states of PDZ binding motif, and a variant containing glycines in place of the last four, C-terminal amino acids (4G), were studied.
X
ABCC2 p.Ser1542Glu 12615054:143:54
status: NEW164 The binding of the phosphorylation mimicking MRP2 S1542E mutant and the phosphorylated C-terminal peptide to EBP50 changed in our experiments.
X
ABCC2 p.Ser1542Glu 12615054:164:50
status: NEW