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EphB-Ephrin-B Signaling

EphB is a subfamily of the Eph tyrosine kinase (Tk) receptor family composed of six members: EphB1, EphB2, EphB3, EphB4, EphB5, and EphB6. The EphB receptor subfamily interacts with its ligand family, EphrinB, composed of EphrinB1, EphrinB2, and EphrinB3. The EphrinB proteins are transmembrane proteins. EphB and their ligands, EphrinB, are associated with different cells. Consequently, EphB:EphrinB associations mediate inter-cellular (cell:cell) communications. The EphB and the EphrinB families both communicate extracellular signals into the interior of their associated cells making EphB:EphrinB signaling bidirectional. The activation of cell:cell bidirectional signaling through EphB:EphrinB proteins involves the binding of EphB receptors to specific oligomerized EphrinB proteins on juxtapositioned cells.

EphB:EphrinB receptor duets regulate basic cell functions such as cell:cell repulsion and adhesion. Consequently, they are important mediators of tissue structure development. Specific EphB:EphrinB interactions mediate cell:cell recognition and send signals that direct cell attachment, migration and cytoskeletal structure development, especially via the actin cytoskeleton. These processes are important in cell patterning during embryogenesis; neural processes such as axon guidance, neural crest cell migration, and dendritic spike formation and in the patterning of vascular structure.

Bidirectional internal signaling differentially activates several pathways. Both EphB and EphrinB receptors have cytoplasmic C-terminal sequences capable of interacting with PDZ-domain-containing proteins such as: scaffold molecule, protein interacting with C-kinase-1 (PICK1); SNARE protein, syntenin; adapter molecule, glutamate receptor-interacting protein (GRIP) and PDZ-RGS, linking to GPCRs. EphB and EphrinB are able to signal cytoskeletal reorganization through regulation of the Rho-GTPase; RhoA, Rac1 and Cdc42.

References:

Adams, R. H. et. al. (1999) Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 13, 295-306.
Huot, J. (2004) Ephrin signaling in axon guidance. Prog. Neuropsychopharmacol Biol. Psychiatry. 2004 Aug;28(5):813-8.
Wilkinson, D. G. (2000) Eph receptors and ephrins: regulators of guidance and assembly. Int. Rev. Cytol. 196, 177-244.

Content for this page is provided by Dennis R. Conrad, Ph.D., a Life Science industry consultant with over 25 years of experience in the formulation and optimization of cell culture media. Dr. Conrad's email address is biomediaexpert@earthlink.net