FEATURES

FAMILY

DESCRIPTION

Also known as TIE2_HUMAN, TEK, TIE2, VMCM, VMCM1. 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. Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular matrix. Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating cells. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain).

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EXTERNAL LINKS

TEK

Angiopoietin-1 receptor

ligandability Mutations

TEK

Molecular Synopsis