a transmembrane tyrosine-protein kinase receptor for ANGPT1, ANGPT2 and ANGPT4. Regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Expressed almost exclusively in endothelial cells. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. 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 FAK and of the downstream kinases ERK2 and ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. ANGPT2 has lower affinity for TEK, promoting TEK autophosphorylation in the absence of ANGPT1, but inhibiting ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. Three isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 18.104.22.168; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Tie family
Molecular Function: ATP binding; growth factor binding; protein binding; protein kinase activity; protein tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; receptor activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: angiogenesis; cell-cell signaling; endochondral ossification; endothelial cell proliferation; glomerulus vasculature development; heart development; leukocyte migration; MAPK cascade; negative regulation of angiogenesis; negative regulation of apoptosis; negative regulation of endothelial cell apoptotic process; negative regulation of inflammatory response; peptidyl-tyrosine phosphorylation; positive regulation of actin cytoskeleton reorganization; positive regulation of angiogenesis; positive regulation of endothelial cell migration; positive regulation of endothelial cell proliferation; positive regulation of ERK1 and ERK2 cascade; positive regulation of focal adhesion assembly; positive regulation of intracellular signal transduction; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein kinase B signaling; positive regulation of protein phosphorylation; protein autophosphorylation; protein oligomerization; regulation of endothelial cell apoptotic process; regulation of establishment or maintenance of cell polarity; regulation of vascular permeability; response to cAMP; response to estrogen; response to hypoxia; response to peptide hormone; signal transduction; sprouting angiogenesis; Tie signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway