Title: EphB/ephrinB Signaling in Cell Adhesion and Migration
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. INTRODUCTION1 Growth and maturation of an embryo requires synchronized communication of biochemical signals, which are mediated by protein-protein interactions between ligands and cell-surface receptors in early development.The EphB receptors and ephrinB ligands are cell surface proteins that influence cell behavior during embryogenesis and development (Batlle et al., 2002;Pasquale, 2008;Solanas et al., 2011).Eph receptors are expressed in all embryonic germ layers and mediate various functions, which include directing cell positioning and migration, axon guidance, patterning, and tissue morphogenesis during development.In addition, they also have diverse functions in tissue boundary formation, segmentation, and the development of the vascular system (Lee and Daar, 2009;