Angiopoietin-1 receptor (TIE2) (TEK)

The Angiopoietin-1 receptor, commonly known as TIE2, is a receptor tyrosine kinase (RTK) essential for vascular remodeling, maturation, and stability (UniProt P35590). It is predominantly expressed on endothelial cells and certain hematopoietic stem cells, where it mediates signals from the angiopoietin family of growth factors (PubMed PMID: 28611162). Under physiological conditions, the binding of Angiopoietin-1 (Ang-1) to the TIE2 receptor induces autophosphorylation of the intracellular kinase domain, promoting endothelial cell survival and maintaining vascular integrity. Conversely, Angiopoietin-2 (Ang-2) often acts as a context-dependent antagonist, destabilizing the vasculature to allow for remodeling or pathological angiogenesis in the presence of other factors like VEGF (PubMed PMID: 30333116). In oncology, TIE2 is a target for multi-kinase inhibitors such as Regorafenib and Sorafenib, which aim to disrupt the blood supply to tumors by inhibiting the receptor's catalytic activity (DrugBank DB08896). In ophthalmology, the pathway is targeted to treat neovascular age-related macular degeneration and diabetic macular edema, either by inhibiting Ang-2 or by activating TIE2 through VE-PTP inhibition to reduce vascular leakage (PubMed PMID: 31433916).

Other names

TEK tyrosine kinaseTyrosine-protein kinase receptor TEKTunica interna endothelial cell kinaseCD202Bp140 TEKVMCMVMCM1

Small molecule inhibitors bind to the intracellular kinase domain to competitively inhibit ATP binding, thereby blocking downstream signaling pathways like PI3K/Akt and MAPK that drive angiogenesis (PubMed PMID: 30333116). Alternatively, activation of the receptor via VE-PTP inhibition or ligand modulation promotes vascular stability and reduces permeability (PubMed PMID: 31433916).