TIE1/TIE (tyrosine kinase with Ig and EGF homology domains 1) and TIE2/Tek define a new class of the receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin like domains flanking three epidermal growth factor (EFG) like domains followed by three fibronectin type III like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region. Human TIE1 cDNA encodes a 1138 amino acid residue precursor protein with a putative signal peptide, an extracellular domain, and a cytoplasmic domain. Human TIE1/Fc, a disulfide linked homodimeric protein, has a calculated molecular mass of approximately 107 kDa. Due to glycosylation, the protein migrates to approximately 160 kDa in SDS PAGE under reducing conditions. TIE1 and TIE2, expressed primarily on endothelial and hematopoietic progenitor cells, play important roles in angiogenesis, vasculogenesis, and hematopoiesis. In developing vascular endothelial cells, TIE1 and TIE2 are specifically expressed. Two ligands that bind TIE have been identified, angiopoietin 1 and angiopoietin 2. Based on gene targeting studies, the in vivo functions of TIE1 are related to endothelial cell differentiation. The receptor tyrosine kinase TIE also plays a role in the survival and integrity of the endothelium.