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

Academic Article
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Overview

authors

  • Tzima, E.
  • Reader, J. S.
  • Irani-Tehrani, M.
  • Ewalt, K. L.
  • Schwartz, M. A.
  • Schimmel, Paul

publication date

  • January 2005

journal

  • Journal of Biological Chemistry  Journal

abstract

  • 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.

subject areas

  • 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
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.C400431200

PubMed ID

  • 15579907
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Additional Document Info

start page

  • 2405

end page

  • 2408

volume

  • 280

issue

  • 4

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