title: Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase.
abstract: The first step of protein synthesis is catalyzed by aminoacyl-tRNA synthetases. In addition, certain mammalian tRNA synthetases link protein synthesis to cytokine signaling pathways. In particular, human tyrosyl-tRNA synthetase (TyrRS) can be split by proteolysis into two fragments having distinct cytokine activities. One of the TyrRS fragments (mini TyrRS) contains features identical to those in CXC chemokines (like interleukin-8) that also act as angiogenic factors. Here mini TyrRS (but not full-length TyrRS) is shown to stimulate chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of two in vivo animal models. The angiogenic activity of mini TyrRS can be opposed by anti-angiogenic chemokines like IP-10. Thus, a biological fragment of human tyrosyl-tRNA synthetase links protein synthesis to regulation of angiogenesis.
authors.affiliation: Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wakasugi
authors.forename: Bonnie M
authors.initials: BM
authors.lastname: Slike
authors.forename: John
authors.initials: J
authors.lastname: Hood
authors.forename: Karla L
authors.initials: KL
authors.lastname: Ewalt
authors.forename: David A
authors.initials: DA
authors.lastname: Cheresh
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
mesh_terms: D000481:Allantoin; D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014448:Tyrosine-tRNA Ligase / Q000378:metabolism / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins; D000481:Allantoin; D014448:Tyrosine-tRNA Ligase