Eph receptor tyrosine kinase (Eph)

The Eph family receptors are the largest known subfamily of receptor protein-tyrosine kinases (RTKs), divided into EphA and EphB subclasses based on sequence homology and ligand affinity. Eph receptors are single-pass transmembrane proteins featuring an extracellular ligand-binding domain, a cysteine-rich region and fibronectin repeats, and an intracellular tyrosine kinase domain with associated signaling domains (SAM, PDZ-binding motif)[1][2][5]. Their ligands, called ephrins (ephrin-As: GPI-linked; ephrin-Bs: transmembrane), are also membrane-bound, meaning Eph/ephrin signaling usually requires cell-cell contact[1][2]. Eph receptor signaling underpins critical processes such as axon guidance during neural development, cell migration, tissue boundary formation, immune cell trafficking, angiogenesis, and stem cell differentiation[2][6]. In disease contexts, dysregulated Eph signaling contributes to cancer (especially tumor growth, angiogenesis, metastasis), inflammation, immune system dysfunction, and potentially neurodegeneration and cardiovascular disease[1][5][6]. Therapeutic approaches include kinase inhibitors, antagonistic peptides, and antibody-based strategies targeting specific Eph receptors (e.g., EphA2 in cancer). Key challenges include maintaining specificity and avoiding side effects due to the receptors’ roles in diverse physiological processes[1][5][6].

Other names

Eph receptorEph RTKerythropoietin-producing hepatoma receptorEphA/EphB receptor

Competitive inhibition of kinase activity Disruption of Eph-ephrin binding Inhibition of receptor dimerization, clustering, or downstream signaling