Tie receptor family (TIE)

The Tie receptor family, comprising TIE1 and TIE2 (also known as TEK), represents a specialized group of receptor tyrosine kinases primarily expressed on endothelial cells (Korhonen et al., 2016). These receptors, along with their angiopoietin ligands (ANGPT1, ANGPT2, and ANGPT4), constitute a critical signaling pathway for vascular development, maturation, and homeostasis (Saharinen et al., 2017). TIE2 is the primary signaling receptor, while TIE1 acts as a modulator of TIE2 activity through heterodimerization (Korhonen et al., 2016). Under physiological conditions, ANGPT1-mediated activation of TIE2 promotes vascular stability and endothelial cell survival, whereas ANGPT2 often acts as a context-dependent antagonist, promoting vascular destabilization and permeability in inflammatory or pro-angiogenic environments (Kim et al., 2016). Dysregulation of this pathway is implicated in cancer, where it drives tumor angiogenesis, and in ocular diseases like diabetic retinopathy and age-related macular degeneration (Kaiser, 2019). Therapeutic strategies targeting this system include ANGPT2 inhibitors like faricimab, TIE2 activators such as razuprotafib, and multi-kinase inhibitors like regorafenib, which are often used to enhance vascular normalization and treatment efficacy (Jayson et al., 2016; Saharinen et al., 2017).

Other names

Angiopoietin receptorsTEKTIE1TIE2Tyrosine-protein kinase receptor TIE-1Tyrosine-protein kinase receptor TIE-2TEK tyrosine kinase endothelialTyrosine kinase with immunoglobulin-like and EGF-like domains

Neutralization of ANGPT2, activation of TIE2 signaling, inhibition of TIE2 kinase activity, and inhibition of the negative regulator VE-PTP.