Tie-1/Tie (tyrosine kinase with Ig and EGF homology domains 1) and Tie-2/Tek comprise a receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains and followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region (1). These receptors are expressed primarily on endothelial and hematopoietic progenitor cells and play critical roles in angiogenesis, vasculogenesis and hematopoiesis (2).
Cynomolgus Monkey Tie-2 cDNA encodes a 1124 amino acid (aa) residue precursor protein with a 22 residue putative signal peptide, a 723 residue extracellular domain and a 354 residue cytoplasmic domain. Two ligands, angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), which bind Tie-2 with high-affinity have been identified. Ang-2 has been reported to act as an antagonist for Ang-1. Mice engineered to overexpress Ang-2 or to lack Ang-1 or Tie-2 display similar angiogenesis defects (3).