Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) (TIE1, TIE2)

Tie receptors are a small family of endothelial-specific receptor tyrosine kinases, consisting primarily of Tie1 and Tie2, which are key cell-surface proteins mediating the angiopoietin signaling pathway. Structurally, each Tie receptor features a unique extracellular domain (combining immunoglobulin-like, EGF-like, and fibronectin type III motifs), a single transmembrane segment, and a cytoplasmic tyrosine kinase domain essential for signal transduction. Tie2 is the principal receptor for angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2), orchestrating vascular growth, stability, permeability, and homeostasis. Tie1, although not a direct ligand-binding receptor, modulates Tie2 signaling and contributes to inflammatory and angiogenic responses, particularly in disease states like cancer or atherosclerosis. The Tie/angiopoietin pathway is critically involved in vascular development and remodeling, making Tie1 and Tie2 major targets for therapeutic intervention in oncology, cardiovascular, inflammatory, and ocular disorders. Experimental and clinical drug development is ongoing, including both agonist and antagonist modalities targeting these receptors.

Other names

TIE receptor familyAngiopoietin receptorTEK receptor tyrosine kinase (for TIE2)RTK class XI (TIE receptor family)

Agonism: Activation of Tie2 by recombinant ANG1 or engineered antibodies to support vascular stability Antagonism: Blocking ANG2 to reduce pathological vessel permeability and angiogenesis Inhibition: Targeting downstream kinases or interacting phosphatases to modulate angiopoietin–Tie signaling