Extended Data Fig. 10. HS GAGs regulate the Ang/Tie signaling pathway.

HS GAGs utilize two distinct binding modes to promote pathway activation. (a) Endothelial cell-associated HS GAGs recruit agonistic ligands Ang1 and Ang4 to form HS-Ang-Tie2 complexes and elicit downstream signaling. (b) HS GAGs also bind to the orphan receptor Tie1 to promote the Tie1-Tie2 interaction, which maintains Tie2 protein levels and prevents protein turnover at the cell surface to sustain downstream signaling.