The major ligands for Tie2 are Ang1 and Ang2. Ang1 has been considered as the primary activating ligand of Tie2 whereas role of Ang2 remains controversial. Ang2 acts as stimulating in some studies and inhibiting in others. The activity of Ang2 is concentration dependent. Ang2 possesses similar receptor affinity to Ang1 and they both share the same binding site on Tie2. The Ang2 fibrinogen domain is solely responsible for receptor recognition and binding, the coiled-coil motif mediates its oligomerization.