title: EphrinB1 controls cell-cell junctions through the Par polarity complex.
abstract: A body of evidence is emerging that shows a requirement for ephrin ligands in the proper migration of cells, and the formation of cell and tissue boundaries. These processes are dependent on the cell-cell adhesion system, which plays a crucial role in normal morphogenetic processes during development, as well as in invasion and metastasis. Although ephrinB ligands are bi-directional signalling molecules, the precise mechanism by which ephrinB1 signals through its intracellular domain to regulate cell-cell adhesion in epithelial cells remains unclear. Here, we present evidence that ephrinB1 associates with the Par polarity complex protein Par-6 (a scaffold protein required for establishing tight junctions) and can compete with the small GTPase Cdc42 for association with Par-6. This competition causes inactivation of the Par complex, resulting in the loss of tight junctions. Moreover, the interaction between ephrinB1 and Par-6 is disrupted by tyrosine phosphorylation of the intracellular domain of ephrinB1. Thus, we have identified a mechanism by which ephrinB1 signalling regulates cell-cell junctions in epithelial cells, and this may influence how we devise therapeutic interventions regarding these molecules in metastatic disease.
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.forename: Tagvor G
authors.initials: TG
authors.lastname: Nishanian
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mood
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Bong
authors.forename: Ira O
authors.initials: IO
authors.lastname: Daar
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian; D036387:Ephrin-B1 / Q000378:metabolism / Q000502:physiology*; D007365:Intercellular Junctions; D010766:Phosphorylation; D011485:Protein Binding; D019108:Tight Junctions; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D036387:Ephrin-B1; C512643:PARD6B protein, Xenopus; D029867:Xenopus Proteins