Ephrin type-B receptor 4(EPHB4) is also known as HTK, MYK1 and TYRO11,is a member of Eph family. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. EphB4 is expressed preferentially on venous endothelial cells (EC) and inhibits cell-cell adhesion, chemotaxis, and angiogenesis. Opposing effects are induced by signaling through Ephrin-B2 expressed on arterial EC: adhesion, endothelial cell migration, and vessel sprouting. EphB4 singaling contributes to new vascularization by guiding venous EC away from Ephrin-B2 expressing EC. Ephrin-B2 signaling induces arterial EC to migrate towards nascent EphB4 expressing vessels. The combination of forward signaling through EphB4 and reverse signaling through Ephrin-B2 promotes in vivo mammary tumor growth and tumor-associated angiogenesis. EphB4 promotes the differentiation of megakaryocytic and erythroid progenitors but not granulocytic or monocytic progenitors.
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