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Review
, 38 (1), 14-9

EphB/ephrinB Signaling in Cell Adhesion and Migration

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Review

EphB/ephrinB Signaling in Cell Adhesion and Migration

Inji Park et al. Mol Cells.

Abstract

Eph receptors and their ligands, ephrins, represent the largest group of the receptor tyrosine kinase (RTK) family, and they mediate numerous developmental processes in a variety of organisms. Ephrins are membrane-bound proteins that are mainly divided into two classes: A class ephrins, which are linked to the membrane by a glycosylphosphatidylinositol (GPI) linkage, and B class ephrins, which are transmembrane ligands. Based on their domain structures and affinities for ligand binding, the Eph receptors are also divided into two groups. Trans-dimerization of Eph receptors with their membrane-tethered ligands regulates cell-cell interactions and initiates bidirectional signaling pathways. These pathways are intimately involved in regulating cytoskeleton dynamics, cell migration, and alterations in cellular dynamics and shapes. The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling. In this review, we present an in-depth overview of the structure, mechanisms, cell signaling, and functions of EphB/ephrinB in cell adhesion and migration.

Keywords: EphB; cell adhesion; cell migration; development; ephrinB.

Figures

Fig. 1.
Fig. 1.
Phosphorylation-dependent EphB/ephrinB signaling. EphB binds to ephrinB, which has a short cytoplasmic region for reverse signaling. Forward signaling by the EphB receptor requires ligand binding and controls actin remodeling, cell migration, cell-cell adhesion, and other developmental events through the recruitment of various interacting molecules to EphB receptor. In addition, ephrinB reverse signaling is accomplished by receptor-ligand binding and phosphorylation of tyrosine residues on ephrinB1 cytoplasmic domain. Phosphorylated ephrinB recruits various interacting proteins to modulate many biological processes including cell adhesion, migration, and gene expressions.
Fig. 2.
Fig. 2.
Phosphorylation-independent ephrinB1 signaling. EphrinB1 promotes cell migration through the activation of Wnt/PCP pathway by interacting with CNK1 and Dsh. In addition, ephrinB1 interacts Par-6, and sequentially releases Cdc42-GTP from intact Par polarity complex, which has a major role in stabilizing TJs. Finally, accumulation of unphosphorylated ephrinB1 in TJs causes disruption of TJs and cell adhesion.

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