C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins
C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins
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DOI：
10.1016/s0006-291x(03)00196-7
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发表时间：
2003-03-14
影响因子：
3.1
通讯作者：
Sarkadi, B
中科院分区：
文献类型：
--
作者：
Hegedüs, T;Sessler, T;Sarkadi, B
MRP2是ABC蛋白超家族的成员，是上皮细胞顶膜阴离子偶联物的atp依赖性输出泵。据报道，MRP2的贩运是由PKC调节的。在可能参与MRP2靶向的c端PDZ结合基序附近，我们发现了一个潜在的PKC磷酸化位点Ser（1542）。因此，我们研究了MRP2及其磷酸化模拟突变体与不同PDZ蛋白（EBP50、E3KARP、PDZK1、ippp、β 2-syntrophin和SAP-97）的相互作用。这些PDZ蛋白与CFTR和ABCA1等具有PDZ结合基序的ABC蛋白的结合也进行了研究。我们观察到顶端定位的PDZ蛋白与MRP2和CFTR的强结合，而β 2-syntrophin仅与ABCA1结合。磷酸化模拟MRP2突变体和磷酸化的c端MRP2肽与ippp、EBP50和EBP50的两个个体PDZ结构域的结合显著增加。我们的研究结果表明，MRP2的PDZ结合基序的磷酸化对MRP2的PDZ结合有深远的影响。(C) 2003年Elsevier Science（美国）出版。
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. (C) 2003 Published by Elsevier Science (USA).