Abstract
Cell‐surface glycosaminoglycans (GAGs) dictate cellular function through their interactions with soluble ligands and transmembrane receptors. However, their importance in signal transduction is often overlooked due to the difficulty in identifying new protein‐glycan binding events. Using a combination of biochemical, computational, and chemical biology techniques, we have examined the possible roles of GAGs to modulate the Ang/Tie signaling axis, a key regulator of vascular development and maintenance. Our combined approach revealed that heparin/heparan sulfate (HS) binds to both the Ang1 and Ang4 ligands and potentiates downstream activation through the formation of a ternary complex with the Tie2 receptor. Moreover, we discovered that HS also interacts with the orphan receptor Tie1, the first evidence of a ligand for this receptor since its discovery nearly 25 years ago. Together, these results reveal novel mechanisms by which sulfated polysaccharides modulate an important endothelial signaling pathway.Support or Funding InformationNational Institutes of Health (R01‐GM093627); National Science Foundation Graduate Research Fellowship (DGE‐1144469)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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