Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. 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 PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/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. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits 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. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1, SHC1 and TIE1.
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TIE2: a receptor tyrosine kinase of the Tie family. Receptor for angiopoietin 1. Expressed almost exclusively in endothelial cells. May constitute the earliest mammalian endothelial cell lineage marker. Appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis. TEK is closely related to the TIE receptor tyrosine kinase.
Protein type: EC 220.127.116.11; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Tie family
Cellular Component: actin filament; apical plasma membrane; basal plasma membrane; basolateral plasma membrane; cell surface; integral to membrane; integral to plasma membrane; intercellular junction; lipid raft; microvillus; perinuclear region of cytoplasm; stress fiber
Molecular Function: growth factor binding; protein binding; protein-tyrosine kinase activity; receptor activity
Biological Process: angiogenesis; cell-cell adhesion; cell-matrix adhesion; endothelial cell proliferation; heart development; hemopoiesis; negative regulation of angiogenesis; negative regulation of apoptosis; patterning of blood vessels; peptidyl-tyrosine phosphorylation; positive regulation of angiogenesis; positive regulation of cell adhesion; positive regulation of cytokine secretion during immune response; positive regulation of focal adhesion formation; positive regulation of peptidyl-serine phosphorylation; positive regulation of phosphoinositide 3-kinase activity; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein amino acid phosphorylation; positive regulation of protein import into nucleus; positive regulation of protein kinase B signaling cascade; positive regulation of vascular endothelial growth factor receptor signaling pathway; protein amino acid autophosphorylation; protein oligomerization; regulation of angiogenesis; regulation of cell migration; regulation of endothelial cell proliferation; regulation of establishment and/or maintenance of cell polarity; response to estrogen stimulus; response to retinoic acid; sprouting angiogenesis; Tie receptor signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway; vasculogenesis
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