EFNB2

Ephrin-B2 (EFNB2), also known as HTKL or LERK5, is a transmembrane ligand belonging to the ephrin family that binds preferentially to EphB receptors. It mediates bidirectional cell-cell signaling critical for vascular development, axon guidance, and tissue boundary formation. Structurally, EFNB2 contains a conserved extracellular Eph-binding domain and a cytoplasmic PDZ-binding motif enabling reverse signaling. Its interactions regulate cytoskeletal dynamics and cell adhesion through Rho GTPase activation. Key pathways influenced by EFNB2 include Eph/ephrin signaling, VEGF-mediated angiogenesis, and Notch cross-talk, with roles in embryonic vascular patterning and tumor neovascularization.
Dysregulation of EFNB2 is implicated in cancers (e.g., glioblastoma, breast cancer), arterial malformations, and neurological disorders. Overexpression promotes tumor angiogenesis and metastasis via EphB4 receptor activation. Therapeutic strategies targeting EFNB2-EphB4 axis include monoclonal antibodies (e.g., sEphB4-HSA in Phase I/II trials for solid tumors) and small-molecule inhibitors disrupting receptor-ligand binding. Recent studies explore EFNB2's potential in regenerative medicine, particularly in vascular graft engineering. Despite challenges in pathway complexity, EFNB2 remains a prioritized target for anti-angiogenic and anti-metastatic therapies.