ANGPT1
This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2015]
Function
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.
Biological Process
Activation of transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
Angiogenesis Source: GO_Central
Cell differentiation Source: UniProtKB-KW
Cell-substrate adhesion Source: Ensembl
Glomerulus vasculature development Source: UniProtKB
Hemopoiesis Source: Ensembl
Heparin biosynthetic process Source: UniProtKB
In utero embryonic development Source: Ensembl
Leukocyte migration Source: Reactome
MAPK cascade Source: Reactome
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cell adhesion Source: UniProtKB
Negative regulation of cytokine production involved in immune response Source: Ensembl
Negative regulation of endothelial cell apoptotic process Source: UniProtKB
Negative regulation of neuron apoptotic process Source: Ensembl
Negative regulation of protein import into nucleus Source: Ensembl
Negative regulation of protein phosphorylation Source: Ensembl
Negative regulation of vascular permeability Source: UniProtKB
Positive chemotaxis Source: UniProtKB
Positive regulation of blood-brain barrier permeability Source: ARUK-UCL
Positive regulation of blood vessel endothelial cell migration Source: UniProtKB
Positive regulation of cell adhesion Source: Ensembl
Positive regulation of endothelial cell migration Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of peptidyl-serine phosphorylation Source: Ensembl
Positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
Positive regulation of protein kinase B signaling Source: UniProtKB
Positive regulation of protein phosphorylation Source: ARUK-UCL
Positive regulation of protein ubiquitination Source: UniProtKB
Positive regulation of receptor internalization Source: UniProtKB
Protein localization to cell surface Source: UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
Regulation of macrophage migration inhibitory factor signaling pathway Source: Ensembl
Regulation of protein binding Source: Ensembl
Regulation of skeletal muscle satellite cell proliferation Source: UniProtKB
Regulation of tumor necrosis factor production Source: Ensembl
Sprouting angiogenesis Source: UniProtKB
Tie signaling pathway Source: UniProtKB