EFNB2

EFNB2 is a human gene that encodes ephrin-B2, a membrane-anchored ligand in the ephrin family. Ephrin-B2 binds to members of the Eph receptor tyrosine kinase family, most notably EphB4, to regulate cell signaling involved in vascular development, neural guidance, and tissue organization. The interaction between ephrin-B2 and Eph receptors mediates bidirectional signaling, meaning signals can propagate both through the receptor-expressing cell (forward signaling) and through the ephrin-expressing cell (reverse signaling).

The ephrin-B2 protein is a type I transmembrane protein with an extracellular domain that engages Eph receptors and a short cytoplasmic tail that contains motifs capable of recruiting signaling partners. This cytoplasmic region enables reverse signaling in cells expressing ephrin-B2, while binding to Eph receptors activates forward signaling in the receptor-expressing cell. EFNB2 is primarily expressed in arterial endothelial cells during development, and its interaction with EphB receptors regulates arterial-venous differentiation, boundary formation, and vascular remodeling. EphB4, commonly expressed by venous endothelium, forms a complementary signaling axis with ephrin-B2 in arterial-venous patterning.

In vivo studies, particularly in mice, show that loss of EFNB2 disrupts angiogenesis and arterial-venous specification, often resulting in embryonic lethality, underscoring its essential role in vascular development. EFNB2 also has roles in lymphatic development and has been investigated in the context of neural development and tissue patterning. Clinically, dysregulation of Eph-ephrin signaling, including EFNB2, has been linked to vascular malformations and to tumor angiogenesis, making the pathway a focus of research for therapeutic modulation.