Table 1.
Angiogenesis-associated activities of aminoacyl-tRNA synthetases. Aminoacyl-tRNA synthetases (ARSs) are subdivided based on whether they elicit angiogenesis-based responses outside the cell, inside the cell, or are ARS-associated proteins. Effects on angiogenesis are reported as “Pro” for pro-angiogenic responses (i.e., stimulate new blood vessel growth), “static” for angiostatic responses (i.e., inhibit new blood vessel growth), and “Anti” for anti-angiogenic responses (i.e., reduce current number of vessels).
| ARS or Associated Factor | Location of Angiogenic Function | Effect on Angiogenesis | Associated Domains | Details |
|---|---|---|---|---|
| Externally Acting ARS | ||||
| YARS | Extracellular | Pro | ELR motif, EMAP II-like [12,13] | Secreted and cleaved into N and C cytokine fragments; N-terminal ELR stimulates angiogenesis; C-terminus may possess EMAP II-like signaling [12,13,14,15] |
| WARS | Extracellular | Static | WHEP domain [16] | Secreted and WHEP-domain removed by secretion or alternative splicing; loss of WHEP-domain allows for interactions with E-cadherin [16,17,18,19] |
| TARS | Extracellular | Pro | Catalytic domain (possibly others) [20] | Secreted and stimulates vessel migration, patterning, and maturation; Based on borrelidin binding site, the mechanism is likely dependent, at least partially, on the catalytic domain [20,21] |
| Internally Acting ARS | ||||
| SARS | Nucleus | Static | NLS [22,23,24] | Directed to nucleus by NLS; Binds to vegfaa promoter and disrupts cMyc induction of vegfaa mRNA [22,23,24] |
| EPRS | Cytoplasm | Static | Three WHEP domains [25] | IFNγ stimulates the release of EPRS from the MSC and its association with the GAIT complex; complex binds to mRNA 3' elements and inhibits translation [25,26,27,28,29,30,31,32] |
| ARS Associated Factors | ||||
| AIMP1 | Extracellular | Pro (low conc.) Anti (high conc.) | EMAP II [33] | Released from MSC in response to apoptotic signals; secreted as full-length AIMP1 or EMAP II; stimulates angiogensis at low concentrations but induces EC apoptosis at high concentrations [33,34,35,36,37,38,39,40,41] |
AIMP1: Aminoacyl-tRNA synthetase interacting multifunctional protein 1; ARS: Aminoacyl-tRNA synthetases; EC: Endothelial cell; ELR: Glutamate-leucine-arginine sequence motif; EMAP II: endothelial monocyte activating polypeptide II; EPRS: Glutamyl-prolyl-tRNA synthetase; GAIT: interfere-γ-activated inhibitor of translation; IFNγ: Interferon-γ; NLS: Nuclear localization signal; SARS: Seryl-tRNA synthetase; TARS: Threonyl-tRNA synthetase; WARS: Tryptophanyl-tRNA synthetase; WHEP-domain: A unique domain named or its association with tryptophanyl-, histidyl-, and glutamyl-prolyl-tRNA synthetases; YARS: Tyrosyl-tRNA synthetase.