ANGPT1
Description
The ANGPT1 (angiopoietin 1) is a protein-coding gene located on chromosome 8.
Angiopoietin 1 (ANGPT1) is a protein encoded by the ANGPT1 gene. Angiopoietins play critical roles in vascular development and angiogenesis. ANGPT1 activates the TEK/TIE2 receptor, a tyrosine-protein kinase receptor specific to endothelial cells, by inducing its tyrosine phosphorylation. This protein is a secreted glycoprotein that contributes to blood vessel maturation and stability and may be involved in the early development of the heart. During pregnancy, angiopoietins complement the VEGF system, supporting endothelial cell survival and vessel remodeling. Knockout models in mice embryos have demonstrated that ANGPT1 is essential for normal development, as embryos lacking ANGPT1 exhibit abnormalities by day 11 and die by day 12.5 of pregnancy.
ANGPT1 binds and activates the TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. This activation plays a crucial role in regulating angiogenesis, promoting endothelial cell survival, proliferation, migration, adhesion, cell spreading, and the reorganization of the actin cytoskeleton. It also contributes to the maintenance of vascular quiescence. ANGPT1 is essential for normal angiogenesis and heart development during embryogenesis. After birth, its role in angiogenesis can be either stimulatory or inhibitory depending on the specific context. In quiescent vessels with tightly connected endothelial cells, ANGPT1 inhibits angiogenesis and promotes vascular stability. It does this by recruiting TEK to cell-cell contacts, forming complexes with TEK molecules from adjacent cells, which preferentially activates the phosphatidylinositol 3-kinase and AKT1 signaling pathways. In contrast, migrating endothelial cells lacking cell-cell adhesions recruit TEK to contacts with the extracellular matrix. This leads to the formation of focal adhesion complexes, activation of PTK2/FAK and downstream kinases MAPK1/ERK2 and MAPK3/ERK1, ultimately stimulating sprouting angiogenesis. ANGPT1 mediates blood vessel maturation and stability, and it is implicated in endothelial developmental processes distinct from those of VEGF. ANGPT1 appears to play a vital role in mediating reciprocal interactions between the endothelium and its surrounding matrix and mesenchyme.
ANGPT1 is also known as AGP1, AGPT, AGPT-1, ANG1, HAE5.
