ANGPT1: Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme.
Protein type: Secreted, signal peptide; Secreted
Chromosomal Location of Human Ortholog: 8q23.1
Cellular Component: extracellular region; extracellular space; intracellular; lipid raft; microvillus; plasma membrane
Molecular Function: protein binding; Ras guanyl-nucleotide exchange factor activity; receptor tyrosine kinase binding
Biological Process: cell differentiation; cell-substrate adhesion; hemopoiesis; heparin biosynthetic process; in utero embryonic development; leukocyte migration; MAPKKK cascade; negative regulation of apoptosis; negative regulation of cell adhesion; negative regulation of cytokine secretion during immune response; negative regulation of neuron apoptosis; negative regulation of protein amino acid phosphorylation; negative regulation of protein import into nucleus; negative regulation of vascular permeability; positive chemotaxis; positive regulation of blood vessel endothelial cell migration; positive regulation of cell adhesion; positive regulation of GTPase activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein kinase B signaling cascade; positive regulation of protein ubiquitination; positive regulation of receptor internalization; regulation of endothelial cell proliferation; regulation of I-kappaB kinase/NF-kappaB cascade; regulation of protein binding; regulation of satellite cell proliferation; regulation of tumor necrosis factor production; sprouting angiogenesis; Tie receptor signaling pathway; transmembrane receptor protein tyrosine kinase activation (dimerization)
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