Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis

Angiopoietin (Ang) 1 is a ligand for endothelium-specific receptor tyrosine kinase Tie-2. In adult vasculature, Ang1/Tie2 signaling is thought to regulate both maintenance of vascular quiescence and promotion of angiogenesis. However, it has been unknown how Tie2 signal regulates these distinct biological functions. Recently, we and Alitalo's group have clarified that Ang1 assembles distinct Tie2 signaling complexes in either presence or absence of endothelial cell-cell adhesions. Ang1 induces trans-association of Tie2 at cell-cell contacts, whereas Tie2 is anchored to the extracellular matrix (ECM) by Ang1 at the cell-substratum interface. Trans-associated Tie2 and ECM-anchored Tie2 activate distinct signaling pathways. In this review, we discuss how Ang1/Tie2 signal regulates both maintenance of vascular quiescence and promotion of angiogenesis, especially focusing on the roles of trans-associated Tie2 and ECM-anchored Tie2.