Background:

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. 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. 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.