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

Tamás Hegedüs, Tamás Sessler, Robert Scott, William Thelin, Éva Bakos, András Váradi, Katalin Szabó, László Homolya, Sharon L. Milgram, Balázs Sarkadi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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 (Ser1542). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, β2-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 β2-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.

Original languageEnglish
Pages (from-to)454-461
Number of pages8
JournalBiochemical and biophysical research communications
Volume302
Issue number3
DOIs
Publication statusPublished - Mar 14 2003

Keywords

  • MRP2
  • PDZ
  • Phosphorylation
  • Protein-protein interaction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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