title: Inhibition of mini-TyrRS-induced angiogenesis response in endothelial cells by VE-cadherin-dependent mini-TrpRS.
abstract: To clarify whether a VE-cadherin-dependent pathway allows mini-TrpRS to inhibit mini-TrpRS-induced new blood vessel formation in endothelial cells (ECs), the inhibitory effects of mutant mini-TrpRS and VE-cadherin on mini-TrpRS-induced angiogenesis were investigated. The effects of mini-TyrRS and mini-TrpRS on EC proliferation were evaluated using an MTT colorimetric assay. Cell migration was assayed using a modified Boyden chamber technique. The angiogenic activity in vitro was evaluated by transwell migration assay and matrigel-induced capillary tube formation. It was found that mini-TrpRS does not inhibit the mini-TyrRS-induced proliferation and migration of EC under the condition of VE-cadherin knockout. While wild-type mini-TrpRS inhibited mini-TyrRS-induced angiogenesis, this activity vanished for the mutant protein. Also, the promotion of angiogenesis by mini-TyrRS and the inhibition of angiogenesis by  mini-TrpRS were VEGFR2 dependent but not VEGF dependent. Mini-TyrRS was able to increase the protein expression of VEGFR-2 in the presence of VE-cadherin, while no stimulatory effect of mini-TyrRS was detected when VE-cadherin was not present. Angiogenesis is therefore stimulated by mini-TyrRS and inhibited by mini-TrpRS, raising the possibility that mini-TyrRS and mini-TrpRS stimulate a common downstream signaling event: VE-cadherin. Thus, naturally occurring fragments of the two proteins involved in translation, TyrRS and TrpRS, have opposing activities on angiogenesis. The opposing activities of the two tRNA synthetases suggest tight regulation of the balance between pro- and antiangiogenic stimuli.
authors: Department of Cardiology, West China Hospital, School of Clinic Medicine, Sichuan University, Chengdu 610041, China.
authors: Rui
authors: R
authors: Zeng
authors: Yu-cheng
authors: YC
authors: Chen
authors: Zhi
authors: Z
authors: Zeng
authors: Xiao-xia
authors: XX
authors: Liu
authors: Rui
authors: R
authors: Liu
authors: Ou
authors: O
authors: Qiang
authors: Xian
authors: X
authors: Li
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014369:Tryptophan-tRNA Ligase / Q000235:genetics / Q000494:pharmacology*; D014448:Tyrosine-tRNA Ligase / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D015820:Cadherins; D010446:Peptide Fragments; D014369:Tryptophan-tRNA Ligase; D014448:Tyrosine-tRNA Ligase; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; C529161:mini-TyrRS, human