Ephrin type-B receptor 6 (EPHB6)

Ephrin type-B receptor 6 (EPHB6) is an atypical receptor of the Eph receptor tyrosine kinase family, lacking intrinsic catalytic activity due to a kinase-inactive domain[1][2]. It binds ephrin-B ligands (notably ephrin-B2) with lower affinity than other EphB receptors, and requires co-receptors (other Eph family members) for signaling function. EPHB6 is involved in diverse biological processes including embryonic development, neuronal signaling, immune responses, vasculogenesis, and most notably, regulates tumor initiation, progression, and metastasis. Structural studies show it adopts a similar architecture to other Eph receptors but possesses unique features (e.g., an 11-serine insertion in the ligand-binding domain) that may affect ligand binding and heterooligomerization with other Eph receptors[1][2]. EPHB6’s atypical, kinase-defective nature underlies its requirement for interaction with other Eph family proteins to participate in downstream signaling, distinguishing its mechanism of action within this receptor class. [1][2]

Other names

EphB6HEPTyrosine-protein kinase-defective receptor EPH-6human kinase-defective Eph-family receptor protein

Drugs targeting EPHB6 would likely modulate cell signaling via the ephrin-Eph receptor pathway, affecting cell adhesion, migration, and invasion. Because EPHB6 is kinase-defective, its signaling requires heterooligomerization with kinase-active Eph receptors to transduce signals[1][2].