Ephrins and Eph Receptors

he erythropoietin-producing hepatocellular (EPH) receptors represent the largest known family of receptor tyrosine kinases and are activated by interactions with cell-surface ligands, termed EFNs. EPH receptors have been classified into two subfamilies, EPHA and EPHB, according to their preference for either glycosylphosphatidylinositol (GPI)-anchored EFN-A ligands or transmembrane EFN-B ligands. Thus far, 14 vertebrate receptors and eight ligands have been identified. All the ligands share a conserved core sequence of approximately 125 amino acids, including 4 invariant cysteine residues, probably corresponding to a receptor binding domain. This is followed by a membrane anchorage domain, taking the form of a GPI anchor for five of the ligands (ephrin-A1 to -A5) or a transmembrane domain for three of them (ephrin-B1 to -B3).