A human aminoacyl-tRNA synthetase as a regulator of angiogenesis.
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.
Wakasugi
Keisuke
K
The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Slike
Bonnie M
BM
Hood
John
J
Otani
Atsushi
A
Ewalt
Karla L
KL
Friedlander
Martin
M
Cheresh
David A
DA
Schimmel
Paul
P
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D012171:Retinal Vessels / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004338:Drug Combinations; D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D007371:Interferon-gamma; D003094:Collagen; D014369:Tryptophan-tRNA Ligase