ISOLATION OF ANGIOPOIETIN-1, A LIGAND FOR THE TIE2 RECEPTOR, BY SECRETION-TRAP EXPRESSION CLONING

TIE2 is a receptor-like tyrosine kinase expressed almost exclusively i n endothelial cells and early hemopoietic cells and required for the n ormal development of vascular structures during embryogenesis. We repo rt the identification of a secreted ligand for TIE2, termed Angiopoiet in-1, using a novel expression cloning technique that involves intrace llular trapping and detection of the ligand in COS cells. The structur e of Angiopoietin-1 differs from that of known angiogenic factors or o ther ligands for receptor tyrosine kinases. Although Angiopoietin-1 bi nds and induces the tyrosine phosphorylation of TIE2, it does not dire ctly promote the growth of cultured endothelial cells. However, its ex pression in close proximity with developing blood vessels implicates A ngiopoietin-1 in endothelial developmental processes.