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A natural fragment of an enzyme that catalyzes the first step of protein synthesis-human tryptophanyl-tRNA synthetase (T2-TrpRS) has potent anti-angiogenic activity. A cellular receptor through which T2-TrpRS exerts its anti-angiogenic activity has not previously been identified. Here T2-TrpRS was shown to bind at intercellular junctions of endothelial cells (ECs). Using genetic knock-outs, binding was established to depend on VE-cadherin, a calcium-dependent adhesion molecule, which is selectively expressed in ECs, concentrated at adherens junctions, and is essential for normal vascular development. In contrast, T2-TrpRS binding to EC junctions was not dependent on platelet endothelial cell adhesion molecule type-1, another adhesion molecule found at EC junctions. Pull-down assays confirmed direct complex formation between T2-TrpRS and VE-cadherin. Binding of T2-TrpRS inhibited VEGF-induced ERK activation and EC migration. Thus, a VE-cadherin-dependent pathway is proposed to link T2-TrpRS to inhibition of new blood vessel formation.

Original publication




Journal article


J Biol Chem

Publication Date





2405 - 2408


Amino Acyl-tRNA Synthetases, Angiogenesis Inhibitors, Animals, Antigens, CD, Aorta, Blotting, Western, Cadherins, Cattle, Cell Movement, Cells, Cultured, Cytokines, Endothelium, Vascular, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Gap Junctions, Green Fluorescent Proteins, Immunoprecipitation, Microscopy, Confocal, Microscopy, Fluorescence, Neovascularization, Pathologic, Protein Binding, Recombinant Proteins, Signal Transduction, Tryptophan-tRNA Ligase, Vascular Endothelial Growth Factor A