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Updated: Aug 20, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

VE-cadherin links tRNA synthetase cytokine to anti-angiogenic function

Eleni Tzima1, John S Reader, Mohamad Irani-Tehrani

  • 1Skaggs Institute for Chemical Biology, Department of Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. etzima@scripps.edu

The Journal of Biological Chemistry
|December 8, 2004
PubMed

Insights

A fragment of human tryptophanyl-tRNA synthetase (T2-TrpRS) inhibits new blood vessel formation by binding to VE-cadherin on endothelial cells. This interaction blocks key signaling pathways, revealing a novel anti-angiogenic mechanism.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The enzyme fragment human tryptophanyl-tRNA synthetase (T2-TrpRS) exhibits anti-angiogenic properties.
  • The specific cellular receptor mediating T2-TrpRS anti-angiogenic activity was previously unknown.

Purpose of the Study:

  • To identify the cellular receptor for T2-TrpRS.
  • To elucidate the mechanism by which T2-TrpRS inhibits angiogenesis.

Main Methods:

  • Investigated T2-TrpRS binding to endothelial cells (ECs).
  • Utilized genetic knock-outs to determine the role of VE-cadherin and PECAM-1 in T2-TrpRS binding.
  • Performed pull-down assays to confirm direct complex formation.
  • Assessed the impact of T2-TrpRS binding on VEGF-induced ERK activation and EC migration.

Main Results:

  • T2-TrpRS binds to intercellular junctions of ECs.
  • Binding is dependent on VE-cadherin, an EC-specific adhesion molecule, but not PECAM-1.
  • Direct complex formation between T2-TrpRS and VE-cadherin was confirmed.
  • T2-TrpRS binding inhibited VEGF-induced ERK activation and EC migration.

Conclusions:

  • VE-cadherin serves as the cellular receptor for T2-TrpRS on ECs.
  • A VE-cadherin-dependent pathway links T2-TrpRS to the inhibition of angiogenesis.
  • T2-TrpRS represents a novel therapeutic target for anti-angiogenic strategies.

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