| Post Translational Modifications | Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-990 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1106 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1100 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1106 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation. |
| Function | Tyrosine-protein kinase that acts as a 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 pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for postnatal 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. |
| Protein Name | Angiopoietin-1 ReceptorEndothelial Tyrosine KinaseHykStk1Tunica Interna Endothelial Cell KinaseTyrosine Kinase With Ig And Egf Homology Domains-2Tyrosine-Protein Kinase Receptor TekTyrosine-Protein Kinase Receptor Tie-2Mtie2P140 TekCd Antigen Cd202b |
| Database Links | Reactome: R-MMU-210993Reactome: -MMU-5673001 |
| Cellular Localisation | Cell MembraneSingle-Pass Type I Membrane ProteinCell JunctionFocal AdhesionCytoplasmCytoskeletonSecretedRecruited To Cell-Cell Contacts In Quiescent Endothelial CellsColocalizes With The Actin Cytoskeleton And At Actin Stress Fibers During Cell SpreadingRecruited To The Lower Surface Of Migrating CellsEspecially The Rear End Of The CellProteolytic Processing Gives Rise To A Soluble Extracellular Domain That Is Secreted |
| Alternative Protein Names | Angiopoietin-1 Receptor proteinEndothelial Tyrosine Kinase proteinHyk proteinStk1 proteinTunica Interna Endothelial Cell Kinase proteinTyrosine Kinase With Ig And Egf Homology Domains-2 proteinTyrosine-Protein Kinase Receptor Tek proteinTyrosine-Protein Kinase Receptor Tie-2 proteinMtie2 proteinP140 Tek proteinCd Antigen Cd202b proteinTek proteinHyk proteinTie-2 proteinTie2 protein |
Information sourced from Uniprot.org
![Anti-CD202b/TEK/TIE-2 nanobody [SAA1254] (STJN000254)](https://cdn11.bigcommerce.com/s-zso2xnchw9/images/stencil/600x533/products/200867/413049/STJN000254-SDS-PAGE-1__18865.1749232560.jpg?c=1 "Anti-CD202b/TEK/TIE-2 nanobody [SAA1254] (STJN000254)")