EphrinEph

Ephrin-Eph signaling refers to the interaction between the Eph family of receptor tyrosine kinases and their membrane-bound ephrin ligands. The Eph family is the largest family of receptor tyrosine kinases dedicated to this mode of signaling and is divided into two subclasses: EphA receptors that preferentially bind glycosylphosphatidylinositol-anchored ephrin-A ligands, and EphB receptors that bind transmembrane ephrin-B ligands. Ephrin-A ligands are GPI-anchored and lack cytoplasmic domains, while ephrin-B ligands are transmembrane and possess intracellular tails capable of signaling.

Signaling is bidirectional: forward signaling occurs in the Eph-expressing cell upon ligand binding and receptor clustering, while reverse signaling occurs in the ephrin-expressing cell and can be triggered by binding to Eph receptors. Both signaling directions typically require clustering of receptor-ligand complexes and can be modulated by endocytosis and intracellular interactions. Downstream pathways include Rho family GTPases (Rac, Rho, Cdc42), Src family kinases, MAPK/ERK, and PI3K-Akt, leading to changes in cytoskeletal dynamics, adhesion, and cell behavior. Eph/ephrin signaling can promote either repulsion or adhesion depending on context and cellular state.

Biological roles are diverse: they are crucial in embryonic development and tissue patterning, including axon guidance, neural mapping, somite boundary formation, and vascular patterning. In adults, this signaling helps maintain tissue architecture, regulate synaptic development, and influence stem cell niches and wound healing. Dysregulation of Eph/ephrin signaling is linked to cancer progression and angiogenesis, making these molecules targets of research for therapies and diagnostic biomarkers. The pathway demonstrates context-dependent effects across development and disease.