Do Aminoacyl-tRNA synthetases have biological functions other than in protein biosynthesis?

Park, Sang Gyu; Kim, Sung Hoon

doi:10.1080/15216540600735974

Cited by 9 publications

(14 citation statements)

References 37 publications

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“…During their long evolution, aminoacyl tRNA synthetases, enzymes that catalyze the first committed step of protein synthesis, have acquired additional functions, including the regulation of transcription and translation, RNA splicing, and cytokine activities in inflammatory and angiogenic signaling pathways [1][2][3][4][5]. Minityrosyl-tRNA synthetase (mini-TyrRS) has recently been shown to stimulate neutrophil activation and chemotaxis in vitro and is angiogenic in endothelial cell cultures, chick chorioallantoic membranes (CAM), and mouse matrigel implants [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Mini‐Tyrosyl‐tRNA Synthetase/Mini‐Tryptophanyl‐tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction

Zeng

Wang

You

et al. 2016

Cardiovascular Therapeutics

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contributed equally and are co-first authors. SUMMARYAims: The purpose of this study was to clarify the effect of mini-tyrosyl-tRNA synthetase/ mini-tryptophanyl-tRNA synthetase (mini-TyrRS/mini-TrpRS) in ischemic angiogenesis in rhesus monkeys with acute myocardial infarction (AMI). Methods: A 27-gauge needle was incorporated percutaneously into the left ventricular myocardium of rhesus monkeys with AMI. All monkeys were randomized to receive adenoviral vector mini-TyrRS/mini-TrpRS, which was administered as five injections into the infarcted myocardium, or saline or ad-null (control groups). The injections were guided by EnSite NavX left ventricular electroanatomical mapping. Mini-TyrRS/mini-TrpRS proteins were detected by Western blot and immunoprecipitation analyses. Microvessel density (MVD) per section was measured using immunostaining with a CD34 monoclonal antibody. Proliferating cardiomyocytes were identified through histological and immunohistochemical analyses. Myocardial perfusion and cardiac function were estimated by G-SPECT. Infarction size was also measured. Results: Western blot analyses showed that compared to the normal zone, the expression level of mini-TyrRS/mini-TrpRS was significantly different in the infarction zone. G-SPECT analysis indicated that the mini-TyrRS group had better cardiac function and myocardial perfusion after the injection of ad-mini-TyrRS than before, while mini-TrpRS injection had a totally opposite effect. After mini-TyrRS was administered, there was less of an infarction zone and more proliferating cardiomyocytes and capillaries in the mini-TyrRS group compared to both of the control groups, and the ad-mini-TrpRS group had a totally opposite effect. Conclusion: These results indicated that angiogenesis could be either stimulated by mini-TyrRS or inhibited by mini-TrpRS.

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Section: Introductionmentioning

confidence: 99%

Effect of Mini‐Tyrosyl‐tRNA Synthetase/Mini‐Tryptophanyl‐tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction

Zeng

Wang

You

et al. 2016

Cardiovascular Therapeutics

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“…ARSs also participate in inflammation, angiogenesis, and apoptosis. (2,3) The non-canonical activities of ARSs depend on the type and cellular location of ARS: tyrosyl-, tryptophanyl-, and lysyl-tRNA synthetases are secreted to trigger signaling pathways; glutamyl-prolyl-and glutaminyl-tRNA synthetases express their non-canonical activities in the cytoplasm, whereas lysyl-and methionyl-tRNA synthetases exert nuclear functions. (4,5) The importance of non-canonical functions of ARSs in the development of human diseases has been shown for many enzymes of this group.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Antibodies Against Tyrosyl-tRNA Synthetase and Its Isolated Cytokine-Like Domain

Kondratiuk

Khoruzenko

Cherednyk

et al. 2013

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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Tyrosyl-tRNA synthetase (TyrRS) is one of the key enzymes of protein biosynthesis. In addition to its basic role, this enzyme reveals some important non-canonical functions. Under apoptotic conditions, the full-length enzyme splits into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. The NH 2 -terminal catalytic fragment, known as miniTyrRS, binds strongly to the CXCchemokine receptor CXCR1 and, like interleukin 8, functions as a chemoattractant for polymorphonuclear leukocytes. On the other hand, an extra COOH-terminal domain of human TyrRS has cytokine activities like those of a mature human endothelial monocyte-activating polypeptide II (EMAP II). Moreover, the etiology of specific diseases (cancer, neuronal pathologies, autoimmune disorders, and disrupted metabolic conditions) is connected to specific aminoacyl-tRNA synthetases. Here we report the generation and characterization of monoclonal antibodies specific to N-and C-terminal domains of TyrRS. Recombinant TyrRS and its N-and C-terminal domains were expressed as His-tag fusion proteins in bacteria. Affinity purified proteins have been used as antigens for immunization and hybridoma cell screening. Monoclonal antibodies specific to catalytic N-terminal module and C-terminal EMAP II-like domain of TyrRS may be useful as tools in various aspects of TyrRS function and cellular localization.

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“…Mini-TyrRS stimulates neutrophil activation and chemotaxis in vitro and is angiogenic in endothelial cell cultures and in chick chorioallantoic membrane (CAM) and mouse matrigel implants (22,(32)(33)(34)(35). Like CXC chemokines, such as IL-8, mini-TyRS has an ELR motif (Glu-Leu-Arg) that confers its chemokine and angiogenic activities.…”

mentioning

confidence: 99%

“…Human tyrosyl-tRNA synthetase (TyrRS), for example, has a carboxyl-terminal domain that is not part of the prokaryotic and lower eukaryotic TyrRS molecules. The synthetase also has an N-terminal domain that is cleaved by several endogenous enzymes, yielding mini-tyrosyl tRNA synthetase (mini-TyrRS).Mini-TyrRS has recently been shown to possess cytokinelike actions, leading to its inclusion in a growing family of aminoacyl tRNA synthetase (AARS) multifunction cytokinelike proteins and peptides (22,(32)(33)(34)(35). Mini-TyrRS stimulates neutrophil activation and chemotaxis in vitro and is angiogenic in endothelial cell cultures and in chick chorioallantoic membrane (CAM) and mouse matrigel implants (22,(32)(33)(34)(35).…”

mentioning

confidence: 99%

“…These data show that mini-TyrRS has dose-dependent biphasic effects on ischemic angiogenesis and vascular permeability in vivo, that is, antiangiogenic and antipermeability activities at low concentration and proangiogenic, propermeability activities at high concentrations. hypoxia; ischemia; vascular endothelial growth factor AMINOACYL-TRNA SYNTHETASES, which catalyze the aminoacylation of tRNA molecules, are essential for encoding genetic information during translation (22,(32)(33)(34)(35). In higher eukaryotes, aminoacyl-tRNA synthetases associate with other polypeptides to form supramolecular multienzyme complexes.…”

mentioning

confidence: 99%

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Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability

Cheng

Zhang

Yang

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Faber JE. Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability. Am J Physiol Regul Integr Comp Physiol 295: R1138 -R1146, 2008. First published August 27, 2008 doi:10.1152/ajpregu.90519.2008, the N-terminal domain of tyrosyl-tRNA synthetase, is a recently identified protein released by endothelial cells that exhibits angiogenic and leukocyte chemoattractant, ELR-motif (Glu-Leu-Arg)-dependent activities in vitro. We sought to determine whether exogenous mini-TyrRS exerts these and other cytokine-like actions in physiological and pathological settings in vivo. High-dose mini-TyrRS (600 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) augmented while low-dose mini-TyrRS (3 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ), unexpectedly, inhibited angiogenesis in the ischemic mouse ear. Enhanced angiogenesis was associated with increased CD45-and CD4-positive leukocyte accumulation. Mini-TyrRS also had biphasic actions on both basal and mustard oil-evoked and VEGF-evoked leakage of Evan's blue dye-albumin in nonischemic ear and in endothelial cell monolayers, that is, low-dose inhibited and high-dose augmented leakage. Mutation of the ELR motif of mini-TyrRS abolished the above activities. Mini-TyrRS was reduced (immunoblot) in extracts of ischemic calf muscle and in thoracic aorta explants exposed to hypoxia or VEGF. Inhibition of VEGF with a soluble Flt1 "trap" protein abolished this hypoxic-induced reduction in mini-TyrRS in aorta explants. These data show that mini-TyrRS has dose-dependent biphasic effects on ischemic angiogenesis and vascular permeability in vivo, that is, antiangiogenic and antipermeability activities at low concentration and proangiogenic, propermeability activities at high concentrations. hypoxia; ischemia; vascular endothelial growth factor AMINOACYL-TRNA SYNTHETASES, which catalyze the aminoacylation of tRNA molecules, are essential for encoding genetic information during translation (22,(32)(33)(34)(35). In higher eukaryotes, aminoacyl-tRNA synthetases associate with other polypeptides to form supramolecular multienzyme complexes. The eukaryotic tRNA synthetases consist of a core enzyme, which is closely related to the prokaryotic counterpart of the tRNA synthetase, and an additional domain that is appended to the amino-terminal or carboxyl-terminal end of the core enzyme. Human tyrosyl-tRNA synthetase (TyrRS), for example, has a carboxyl-terminal domain that is not part of the prokaryotic and lower eukaryotic TyrRS molecules. The synthetase also has an N-terminal domain that is cleaved by several endogenous enzymes, yielding mini-tyrosyl tRNA synthetase (mini-TyrRS).Mini-TyrRS has recently been shown to possess cytokinelike actions, leading to its inclusion in a growing family of aminoacyl tRNA synthetase (AARS) multifunction cytokinelike proteins and peptides (22,(32)(33)(34)(35). Mini-TyrRS stimulates neutrophil activation and chemotaxis in vitro and is angiogenic in endothelial cell cultures and in chick chorioallantoic membrane (CAM) and mouse matrigel implants (22,(32)(33)(34)...

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Do Aminoacyl-tRNA synthetases have biological functions other than in protein biosynthesis?

Cited by 9 publications

References 37 publications

Effect of Mini‐Tyrosyl‐tRNA Synthetase/Mini‐Tryptophanyl‐tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction

Effect of Mini‐Tyrosyl‐tRNA Synthetase/Mini‐Tryptophanyl‐tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction

Monoclonal Antibodies Against Tyrosyl-tRNA Synthetase and Its Isolated Cytokine-Like Domain

Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability

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