Angiopoietin proteins 1 through 4 are all ligands for Tie-2 receptors. Tie-1 heterodimerizes with Tie-2 to enhance and modulate signal transduction of Tie-2 for vascular development and maturation. Tyrosine kinase receptors are typically expressed on vascular endothelial cells and specific macrophages for immune responses. Angiopoietin-1 is a growth factor produced by vascular support cells, specialized pericytes in the kidney, and hepatic stellate cells (ITO) cells in the liver. This growth factor is also a glycoprotein and functions as an agonist for the tyrosine receptor found in endothelial cells. Angiopoietin-1 and tyrosine kinase signaling are essential for regulating blood vessel development and the stability of mature vessels.