Angiopoietin-4

Angiopoietins are a family of vascular growth factors that are ligands for the tyrosine kinase receptor Tie-2. Angiopoietins acts primarily on the vasculature to control blood vessel development and stability. Four distinct angiopoietins have been described: Ang-1, Ang-2, Ang-3 and Ang-4. Structurally, the angiopoietins contain an N-terminal super clustering domain (SCD), a central coiled-coil domain (CCD) responsible for ligand homo-oligomerization, a linker region, and a C-terminal fibrinogen-related domain (FReD) required for binding to the Tie-2 receptor. Angiopoietins bind the second immunoglubulin motif of Tie-2 whereby they activate Tie-2 and, indirectly, Tie-1 in Tie-1/Tie-2 heterodimers. Angiopoietins (ANG1-ANG4) and the Tie-1/2 form an endothelial signalling pathway that is necessary for embryonic cardiovascular and lymphatic development. In adults, this system regulates vascular homeostasis, and controls vessel permeability, inflammation and angiogenic responses. Ang-1 and Ang-2 are the most exhaustively studied angiopoietins. Ang-1 is a critical player in vessel maturation and it mediates migration, adhesion and survival of endothelial cells. Ang-2 disrupts the connections between the endothelium and perivascular cells and promotes cell death and vascular regression.