RRC ID 36739
著者 Nakamoto T, Miyanokoshi M, Tanaka T, Wakasugi K.
タイトル Identification of a residue crucial for the angiostatic activity of human mini tryptophanyl-tRNA synthetase by focusing on its molecular evolution.
ジャーナル Sci Rep
Abstract Human tryptophanyl-tRNA synthetase (TrpRS) exists in two forms: a full-length TrpRS and a mini TrpRS. We previously found that human mini, but not full-length, TrpRS is an angiostatic factor. Moreover, it was shown that the interaction between mini TrpRS and the extracellular domain of vascular endothelial (VE)-cadherin is crucial for its angiostatic activity. However, the molecular mechanism of the angiostatic activity of human mini TrpRS is only partly understood. In the present study, we investigated the effects of truncated (mini) form of TrpRS proteins from human, bovine, or zebrafish on vascular endothelial growth factor (VEGF)-stimulated chemotaxis of human umbilical vein endothelial cells (HUVECs). We show that both human and bovine mini TrpRSs inhibited VEGF-induced endothelial migration, whereas zebrafish mini TrpRS did not. Next, to identify residues crucial for the angiostatic activity of human mini TrpRS, we prepared several site-directed mutants based on amino acid sequence alignments among TrpRSs from various species and demonstrated that a human mini K153Q TrpRS mutant cannot inhibit VEGF-stimulated HUVEC migration and cannot bind to the extracellular domain of VE-cadherin. Taken together, we conclude that the Lys153 residue of human mini TrpRS is a VE-cadherin binding site and is therefore crucial for its angiostatic activity.
巻・号 6
ページ 24750
公開日 2016-4-20
DOI 10.1038/srep24750
PII srep24750
PMID 27094087
PMC PMC4837363
MeSH Amino Acid Substitution Amino Acids* Aminoacylation Animals Binding Sites Cadherins / metabolism Chemotaxis Endothelial Cells / metabolism Enzyme Activation Evolution, Molecular* Humans Protein Binding Tryptophan-tRNA Ligase / chemistry* Tryptophan-tRNA Ligase / genetics* Tryptophan-tRNA Ligase / metabolism Vascular Endothelial Growth Factor A / metabolism
IF 3.998
引用数 6
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
シロイヌナズナ / 植物培養細胞・遺伝子 pda07685