EphB

EphB receptors constitute the B-class subgroup of the Eph receptor tyrosine kinase family and mediate contact-dependent cell-cell communication through interactions with transmembrane ephrin-B ligands, thereby regulating tissue patterning, cell positioning, and developmental morphogenesis^[1][2]. Mechanistically, EphB-ephrin-B engagement induces bidirectional signaling, including forward signaling in receptor-expressing cells and reverse signaling in ligand-expressing cells, which coordinates cytoskeletal remodeling, cell adhesion, cell repulsion, and directed migration^[1][3]. Through these signaling networks, EphB receptors regulate axon guidance, synapse formation, tissue boundary establishment, angiogenesis, and epithelial organization during embryonic and postnatal development^[1][2][4]. In disease-associated contexts, dysregulated EphB signaling has been linked to cancer progression, tumor cell migration, angiogenesis, and alterations in tissue homeostasis, although biological outcomes are highly context dependent^[5][6]. Compared with related EphA family receptors, EphB receptors preferentially interact with ephrin-B ligands and exhibit distinct functions in neuronal connectivity, vascular specification, and bidirectional signaling mechanisms^[1][6]. Among individual isoforms, EphB2 is extensively studied for its roles in excitatory synapse organization and neuronal signaling, whereas EphB4 is particularly associated with vascular development and endothelial cell identity^[4][7]. For experimental applications, recombinant ephrin-B-Fc fusion proteins, soluble receptor ectodomains, and EphB-targeting inhibitors or blocking reagents are widely used to manipulate EphB signaling and investigate cell migration, angiogenesis, neural development, and cancer-related mechanisms^[5][8].