Our hosting provider is experiencing network issues which may result in intermittent downtime. We apologize for any inconveniences this may cause.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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.

Pubmed ID: 12615054

Authors

  • Hegedüs T
  • Sessler T
  • Scott R
  • Thelin W
  • Bakos E
  • Váradi A
  • Szabó K
  • Homolya L
  • Milgram SL
  • Sarkadi B

Journal

Biochemical and biophysical research communications

Publication Data

March 14, 2003

Associated Grants

None

Mesh Terms

  • Amino Acid Motifs
  • Animals
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Humans
  • Insects
  • Mitochondrial Proteins
  • Peptides
  • Phosphorylation
  • Plasmids
  • Protein Binding
  • Protein Structure, Tertiary
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Serine