The Eph Receptor Family

Abstract

Eph receptors constitute the largest subfamily of receptor tyrosine kinases and mediate contact-dependent cell–cell communication in many tissues. Unique features of Eph receptors include their engagement with membrane-attached ephrin ligands, the requirement of higher-order clustering for full activation, and bidirectional signaling into the receptor- as well as ligand-expressing cell. Eph receptor functions can be additionally modulated by cis interactions with ephrins expressed on the same cell as well as proteolytic cleavage. Extensive studies in several model organisms have implicated Eph receptors in multiple physiological and pathological processes at all stages from early embryogenesis to aging. Eph signaling is often repulsive and governs cell sorting, migration, and boundary formation. During embryonic and early postnatal period, Ephs are involved in the development of the nervous system, cardiovascular system, and several other organs and tissues. Eph receptors also have various functions in adult physiology, including their important role in neural plasticity. Finally, Ephs have emerged as important players in different types of cancer and several neurological diseases and are regarded as potential drug targets for these disorders.