Letter abstract
Nature Cell Biology 10, 979 - 986 (2008)
Published online: 6 July 2008 | doi:10.1038/ncb1758
EphrinB1 controls cell–cell junctions through the Par polarity complex
Hyun-Shik Lee1, Tagvor G. Nishanian1, Kathleen Mood1, Yong-Sik Bong1,2 & Ira O. Daar1
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 metastasis1, 2, 3, 4, 5, 6, 7, 8, 9. 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.
- Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.
- Current address: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA.
Correspondence to: Ira O. Daar1 e-mail: daar@ncifcrf.gov
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