TIE

The Tie receptor tyrosine kinase (RTK) family that comprises the Tie1 and Tie2 receptors forms a distinct subfamily among the mammalian RTK families. Of these endothelial tyrosine kinases, Tie2 binds to angiopoietins (Ang, Angpt), while Tie1 is an orphan receptor with no characterized ligand so far. Structurally Tie1 and Tie2 share 70% homology in their intracellular domains, and 30% in their extracellular domains, which consist of epidermal growth factor, immunoglobulin, and fibronectin type III homology domains. The expression of Tie1 and Tie2 is almost exclusively restricted to endothelial cells, and the angiopoietin-Tie system is a significant regulator of both blood and lymphatic vessel development, normal vascular homeostasis, and pathological angiogenesis in tumors. Ang2 expression is elevated in human cancer, and the Ang-Tie system has recently emerged as a potential novel target for anti-angiogenic tumor therapies. Currently, angiopoietin-targeting agents are tested in phase 1-3 clinical oncology trials, also in combination with VEGF-based anti-angiogenic therapies. © Springer Science+Business Media New York 2017. All rights reserved.