A human aminoacyl-tRNA synthetase as a regulator of angiogenesis

Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):173-7. doi: 10.1073/pnas.012602099. Epub 2002 Jan 2.

Abstract

Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis. It was shown recently that human tyrosyl-tRNA synthetase (TyrRS) can be split into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase (TrpRS) is a close homologue of TyrRS. A natural fragment, herein designated as mini TrpRS, was shown by others to be produced by alternative splicing. Production of this fragment is reported to be stimulated by IFN-gamma, a cytokine that also stimulates production of angiostatic factors. Mini TrpRS is shown here to be angiostatic in a mammalian cell culture system, the chicken embryo, and two independent angiogenesis assays in the mouse. The full-length enzyme is inactive in the same assays. Thus, protein synthesis may be linked to the regulation of angiogenesis by a natural fragment of TrpRS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Cell Movement
  • Cells, Cultured
  • Chick Embryo
  • Chorion / metabolism
  • Collagen / pharmacology
  • Drug Combinations
  • Endothelial Growth Factors / metabolism
  • Endothelium, Vascular / cytology
  • Humans
  • Interferon-gamma / pharmacology
  • Laminin / pharmacology
  • Lymphokines / metabolism
  • Mice
  • Neovascularization, Pathologic*
  • Protein Structure, Tertiary
  • Proteoglycans / pharmacology
  • Retinal Vessels / metabolism
  • Signal Transduction
  • Time Factors
  • Tryptophan-tRNA Ligase / chemistry*
  • Tryptophan-tRNA Ligase / genetics
  • Tryptophan-tRNA Ligase / physiology*
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Drug Combinations
  • Endothelial Growth Factors
  • Laminin
  • Lymphokines
  • Proteoglycans
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • matrigel
  • Interferon-gamma
  • Collagen
  • Tryptophan-tRNA Ligase