Recombinant Human Angiopoietin-4 Protein

Human Angiopoietin-4 (Ang-4) (1), alternatively named Ang-3 (2), is a secreted glycoprotein belonging to the angiopoietin family. It has the characteristic structural motifs of angiopoietins including the coiled-coiled domain near the amino-terminus and a fibrinogen-like domain at the C-terminus. Human Ang-4 cDNA encodes a 503 amino acid (aa) precursor protein with a 23 aa signal peptide. It shares 45%, 47% and 54% aa sequence identity with human Ang-1, human Ang-2 and mouse Ang-3, respectively. Although the sequence homology is much higher between the human and mouse counterparts for Ang-1 (97%) and Ang-2 (85%), mouse Ang-3 is believed to be an ortholog of human Ang-4 based on chromosomal localization studies (2). Human Ang-4 is highly expressed in lung and in cultured human umbilical vein endothelial cells (HUVECs). In contrast, mouse Ang-3 is expressed multiple mouse tissues. Human Ang-4 is an agonist that can bind and activate Tie-2, a receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains expressed primarily on endothelial cells and early hematopoietic cells (2, 3). Mouse Ang-3 has been reported to be a Tie-2 antagonist. It is likely that mouse Ang-3, like Ang-2, may exert agonist or antagonist activities depending on the cell context (1, 3, 4).