Phosphorylation of ephrin-B1 via the interaction with claudin following cell-cell contact formation

EMBO J. 2005 Nov 2;24(21):3700-11. doi: 10.1038/sj.emboj.7600831. Epub 2005 Oct 6.


The interaction of the Eph family of receptor protein tyrosine kinase and its ligand ephrin family induces bidirectional signaling via the cell-cell contacts. Although most previous studies have focused on the function of Eph-ephrin pathways in the neural system and endothelial cells, this process also occurs in epithelial and cancer cells, of which the biological involvement is poorly understood. We show that ephrin-B1 creates an in vivo complex with adjacent claudin1 or claudin4 via the extracellular domains of these proteins. The cytoplasmic domain of ephrin-B1 was phosphorylated on tyrosine residues upon the formation of cell-cell contacts, possibly recognizing an intercellular adhesion of claudins. Phosphorylation of ephrin-B1 induced by claudins was abolished by the treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, an inhibitor of the Src family kinases. Moreover, overexpression of ephrin-B1 triggered consequent change in the level of cell-cell adhesion depending on its phosphorylation. These results suggest that ephrin-B1 mediated the cell-cell adhesion of epithelial and cancer cells via a novel Eph receptor-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Adhesion / physiology*
  • Cell Line
  • Chlorocebus aethiops
  • Claudin-1
  • Claudin-4
  • Dogs
  • Enzyme Inhibitors / pharmacology
  • Ephrin-B1 / chemistry
  • Ephrin-B1 / metabolism*
  • Epithelial Cells / physiology
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrimidines / pharmacology
  • Tight Junctions / physiology


  • AG 1879
  • Claudin-1
  • Claudin-4
  • Enzyme Inhibitors
  • Ephrin-B1
  • Membrane Proteins
  • Pyrimidines