ephrin

Ephrin refers to a family of membrane-bound ligands for the Eph receptor tyrosine kinases. In vertebrates, ephrins are divided into two main classes: ephrin-A, which are GPI-anchored, and ephrin-B, which are transmembrane and have a cytoplasmic tail. Eph receptors (EphA and EphB) on neighboring cells bind to ephrins to mediate contact-dependent signaling between adjacent cells.

Binding triggers bidirectional signaling: forward signaling via the Eph receptor causes clustering, autophosphorylation, and downstream pathway activation; reverse signaling through the ligand activates signals in the ephrin-expressing cell. Pathways include Rho family GTPases, MAP kinases, and PI3K/Akt, affecting cytoskeletal dynamics and adhesion.

Ephrin–Eph signaling plays crucial roles in development, including axon guidance and neuronal migration, formation of topographic maps in the visual system, angiogenesis and vascular remodeling, tissue boundary formation, and organogenesis. In the adult, it participates in synaptic plasticity, stem cell niches, and tissue homeostasis.

Ephrin genes are EFNA1-5 and EFNB1-3 in humans; interactions are conserved among vertebrates, with broader presence in metazoans. Eph/ephrin signaling is contact-dependent and can mediate repulsion or adhesion depending on context and receptor–ligand combinations.

Dysregulation of ephrin–Eph signaling is linked to disease, including cancer progression and metastasis, angiogenic disorders, and neurological conditions. Because of its role in cell positioning and vessel formation, the ephrin–Eph system is a focus of therapeutic research, with strategies aimed at modulating signaling in cancer and regenerative medicine.