TI - C - terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins . AB - 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 .