Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 38 (1), 14-9

EphB/ephrinB Signaling in Cell Adhesion and Migration


EphB/ephrinB Signaling in Cell Adhesion and Migration

Inji Park et al. Mol Cells.


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.


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.

Similar articles

  • Eph/ephrin Signalling During Development
    R Klein. Development 139 (22), 4105-9. PMID 23093422. - Review
    Eph receptors and their membrane-tethered ligands have important functions in development. Trans interactions of Eph receptors with ephrins at cell-cell interfaces promot …
  • The Role of Ephrins and Eph Receptors in Cancer
    H Surawska et al. Cytokine Growth Factor Rev 15 (6), 419-33. PMID 15561600. - Review
    Eph receptors are the largest receptor tyrosine kinase family of transmembrane proteins with an extracellular domain capable of recognizing signals from the cells' enviro …
  • Looking Forward to EphB Signaling in Synapses
    S Sloniowski et al. Semin Cell Dev Biol 23 (1), 75-82. PMID 22040917. - Review
    Eph receptors and their ligands ephrins comprise a complex signaling system with diverse functions that span a wide range of tissues and developmental stages. The variety …
  • Eph/ephrin Recognition and the Role of Eph/ephrin Clusters in Signaling Initiation
    DB Nikolov et al. Biochim Biophys Acta 1834 (10), 2160-5. PMID 23628727. - Review
    The Eph receptors and their ephrin ligands play crucial roles in a large number of cell-cell interaction events, including those associated with axon pathfinding, neurona …
  • [Role of Ephrins in Regulation of Tumour Cell Migration]
    E Wybieralska et al. Postepy Biochem 55 (2), 153-62. PMID 19824471. - Review
    Eph receptors are the largest known subfamily of receptor tyrosine kinases. They interact with membrane-bound proteins called ephrins. Recently, an increasing body of evi …
See all similar articles

Cited by 19 PubMed Central articles

See all "Cited by" articles


    1. Adams R. H., Wilkinson G. A., Weiss C., Diella F., Gale N. W., Deutsch U., Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999;13:295–306. - PMC - PubMed
    1. Adams R.H, Diella F., Hennig S., Helmbacher F., Deutsch U., Klein R. The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell. 2001;104:57–69. - PubMed
    1. Arvanitis D.N., Béhar A., Tryoen-Tóth P., Bush J.O., Jungas T., Vitale N., Davy A. Ephrin B1 maintains apical adhesion of neural progenitors. Development. 2013;140:2082–2092. - PubMed
    1. Batlle E., Henderson J.T., Beghtel H., van den Born M.M., Sancho E., Huls G., Meeldijk J., Robertson J., van de Wetering M., Pawson T., et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002;111:251–263. - PubMed
    1. Becker E., Huynh-Do U., Holland S., Pawson T., Daniel T.O., Skolnik E.Y. Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation. Mol. Cell. Biol. 2000;20:1537–1545. - PMC - PubMed

Publication types