Erythropoietin-producing hepatocellular receptor family (Eph receptors)

The Erythropoietin-producing hepatocellular (Eph) receptor family is the largest subfamily of receptor tyrosine kinases (RTKs) [UniProt]. These receptors are activated by membrane-bound ligands called ephrins, leading to unique bidirectional signaling that influences both the receptor-bearing cell (forward signaling) and the ligand-bearing cell (reverse signaling) [Pasquale, 2008]. They are essential during embryonic development for processes such as axon guidance, vascular development, and tissue boundary formation [Kullander & Klein, 2002]. In adults, Eph receptors contribute to physiological processes like synaptic plasticity and angiogenesis, but their dysregulation is linked to various pathologies [Klein, 2012]. In oncology, members like EphA2 and EphB4 are often overexpressed and correlate with poor prognosis, promoting tumor growth, survival, and metastasis [Janes et al., 2014]. Consequently, they are significant therapeutic targets, with several multi-kinase inhibitors already in clinical use and specific antibodies or decoys in development, although their complex signaling roles can lead to context-dependent effects [Boyd et al., 2014].

Other names

Ephrin receptorsEPHEph receptor tyrosine kinases

Inhibition of the intracellular tyrosine kinase domain or disruption of the extracellular interaction between Eph receptors and their membrane-bound ephrin ligands [Boyd et al., 2014].