Angiopoietin-Tie signaling pathway (ANGPT-Tie pathway)

The angiopoietin-Tie signaling pathway comprises a network of glycoprotein ligands (angiopoietin-1, -2, -3, -4, and angiopoietin-like proteins) and two primary receptor tyrosine kinases, Tie1 and Tie2, expressed mainly on endothelial cells. Angiopoietin-1 is a potent Tie2 activator that signals vessel maturation, stability, and protection from leakage and inflammation. Angiopoietin-2, the main antagonist/partial agonist, can destabilize vessels and promote vascular leakage and inflammation—especially in pathological contexts—while also acting as a Tie2 agonist in lymphatic endothelium. Dysregulation of this pathway is implicated in cancer, cardiovascular, inflammatory, infectious, and eye diseases. Therapeutically, drugs targeting Angiopoietin-2 or modulating Tie2 have shown promise in oncology and vascular medicine, either alone or in combination with VEGF inhibitors.

Other names

Angiopoietin pathwayANGPT-Tie receptor pathwayAng/Tie signalingAngiopoietin-Tie2 pathway

Inhibition of ANGPT2 antagonism at Tie2 (restores vascular stability, prevents leak and inflammation); Blockade of vessel destabilization/remodeling in tumors and inflamed tissue; Promotion of quiescence and vessel maturation (through ANGPT1 activation of Tie2); Inhibition of vascular endothelial protein tyrosine phosphatase to increase Tie2 activation.