TIE-2 Protein, Mouse (Inactive, sf9, His-GST)

TIE-2 protein, a tyrosine-protein kinase, acts as a cell-surface receptor for ANGPT1, ANGPT2, and ANGPT4, orchestrating a comprehensive range of processes critical for angiogenesis, endothelial cell survival, proliferation, migration, adhesion, and cell spreading, as well as the maintenance of vascular quiescence. Beyond its essential role in embryonic angiogenesis and heart development, TIE-2 plays a vital role in post-natal hematopoiesis. Its function post-birth involves context-dependent activation or inhibition of angiogenesis. In quiescent vessels, ANGPT1 oligomers recruit TIE-2 to cell-cell contacts, fostering complex formation with neighboring TIE-2 molecules and preferential activation of the phosphatidylinositol 3-kinase and AKT1 signaling cascades, leading to vascular stability. Conversely, in migrating endothelial cells lacking cell-cell adhesions, ANGPT1 recruits TIE-2 to contacts with the extracellular matrix, activating focal adhesion complexes, PTK2/FAK, and downstream kinases MAPK1/ERK2 and MAPK3/ERK1, stimulating sprouting angiogenesis. ANGPT1-triggered TIE-2 signaling involves receptor dimerization and autophosphorylation at specific tyrosine residues, serving as binding sites for scaffold proteins and effectors. Modulation by ANGPT2, which competes for the same binding site, and formation of heterodimers with TIE1, as well as proteolytic processing yielding a soluble extracellular domain, further regulate TIE-2 signaling. The soluble extracellular domain functions as a decoy receptor for angiopoietins, influencing signaling dynamics. TIE-2 phosphorylates DOK2, GRB7, GRB14, PIK3R1, SHC1, and TIE1, underscoring its intricate role in finely tuning a myriad of cellular responses.