title: Dose-dependent biphasic activity of tRNA synthetase-associating factor, p43, in angiogenesis.
abstract: Mammalian aminoacyl tRNA synthetases form a macromolecular protein complex with three non-enzymatic cofactors. Among these factors, p43 is also secreted to work as a cytokine on endothelial as well as immune cells. Here we investigated the activity of p43 in angiogenesis and determined the related mediators. It promoted the migration of endothelial cells at low dose but induced their apoptosis at high dose. p43 at low concentration activated extracellular signal-regulating kinase, which resulted in the induction and activation of matrix metalloproteinase 9. In contrast, p43 at high concentration activated Jun N-terminal kinase, which mediated apoptosis of endothelial cells. These results suggest that p43 is a novel cytokine playing a dose-dependent biphasic role in angiogenesis.
authors.affiliation: National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Korea.
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Young Ha
authors.initials: YH
authors.lastname: Ahn
authors.forename: Soon Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Kwang-Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Ko
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C077219:small inducible cytokine subfamily E, member 1; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D020169:Caspases; D020780:Matrix Metalloproteinase 9; D000604:Amino Acyl-tRNA Synthetases