Molecular cloning, expression, and characterization of angiopoietin-related protein - Angiopoietin-related protein induces endothelial cell sprouting

Using degenerate polymerase chain reaction, we isolated a cDNA encoding a n ovel 493-amino acid protein from human and mouse adult heart cDNAs and have designated it angiopoietin-related protein-2 (ARP2), The NH2-terminal and COOH-terminal portions of ARP2 contain the characteristic coiled-coil domai n and fibrinogen-like domain that are conserved in angiopoietins, ARP2 has two consensus glycosylation sites and a highly hydrophobic region at the NH , terminus that is typical of a secretory signal sequence. Recombinant ARP2 expressed in COS cells is secreted and glycosylated, In human adult tissue s, ARP2 mRNA is most abundant in heart, small intestine, spleen, and stomac h. In rat embryos, ARP2 mRNA is most abundant in the blood vessels and skel etal muscles. Endothelial and vascular smooth muscle cells also contain ARP 2 mRNA, Recombinant ARP2 protein induces sprouting in vascular endothelial cells but does not bind to the Tiel or TieB receptor. These results suggest that ARP2 may exert a function on endothelial cells through autocrine or p aracrine action.