TIE2 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily. Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.1; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Tie family
Chromosomal Location of Human Ortholog: 4 C5|4 43.34 cM
Cellular Component:  apical plasma membrane; basal plasma membrane; basolateral plasma membrane; cell junction; cell surface; cell-cell junction; cytoplasm; cytoskeleton; extracellular region; integral component of membrane; integral component of plasma membrane; membrane; membrane raft; microtubule organizing center; microvillus; perinuclear region of cytoplasm; plasma membrane; receptor complex
Molecular Function:  ATP binding; growth factor binding; kinase activity; nucleotide binding; protein binding; protein kinase activity; protein tyrosine kinase activity; signaling receptor activity; transferase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  angiogenesis; branching involved in blood vessel morphogenesis; cell-cell adhesion; cell-matrix adhesion; endothelial cell proliferation; glomerulus vasculature development; heart development; heart trabecula formation; hemopoiesis; negative regulation of angiogenesis; negative regulation of apoptotic process; negative regulation of endothelial cell apoptotic process; peptidyl-tyrosine phosphorylation; phosphorylation; positive regulation of actin cytoskeleton reorganization; positive regulation of angiogenesis; positive regulation of cell adhesion; positive regulation of cytokine secretion involved in immune response; positive regulation of endothelial cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of focal adhesion assembly; positive regulation of intracellular signal transduction; positive regulation of peptidyl-serine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of protein import into nucleus; positive regulation of protein kinase B signaling; positive regulation of protein phosphorylation; positive regulation of vascular endothelial growth factor receptor signaling pathway; protein autophosphorylation; protein complex oligomerization; protein phosphorylation; regulation of angiogenesis; regulation of cell migration; regulation of endothelial cell proliferation; regulation of establishment or maintenance of cell polarity; regulation of NIK/NF-kappaB signaling; response to estrogen; response to hypoxia; response to retinoic acid; sprouting angiogenesis; substrate adhesion-dependent cell spreading; Tie signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway; vasculogenesis
Reference #:  Q02858 (UniProtKB)
Alt. Names/Synonyms: AA517024; Angiopoietin-1 receptor; Cd202b; endothelial-specific receptor tyrosine kinase; HYK; mTIE2; OTTMUSP00000008261; p140 TEK; RP23-345A23.1; STK1; Tek; Tie-2; Tie2; Tunica interna endothelial cell kinase; Tyrosine-protein kinase receptor TEK; Tyrosine-protein kinase receptor TIE-2
Gene Symbols: Tek
Molecular weight: 125,701 Da
Basal Isoelectric point: 6.31  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  Tyrosine Kinases & Substrates
Select Structure to View Below

TIE2

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene