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. 2014 Dec 19;15(12):23725–23748. doi: 10.3390/ijms151223725

Figure 1.

Figure 1

Mechanisms of angiogenesis by extracellularly acting ARS. Left-Full-length tyrosyl-tRNA synthetase (YARS) is secreted from the cell by an unknown mechanism. Outside the cell it is cleaved by polymorphonuclear leukocyte (PMN)-elastase or other protease molecules into N- and C-terminal fragments which stimulate angiogenesis or immune responses respectively; Center-Full-length tryptophanyl-tRNA synthetase (WARS) or mini-WARS are generated from alternative splicing of WARS mRNA and are subsequently secreted into the extracellular space by unknown mechanisms. Full-length WARS is further processed by PMN-elastase or other proteases to form fragments like mini-WARS. The WARS fragments disrupt endothelial cell–cell contacts and angiogenic signaling molecules, eliciting an angiostatic effect; Right-Full-length threonyl-tRNA synthetase (TARS) is secreted from the cell by unknown processes and stimulates vessel migration. The mechanisms of these effects have yet to be determined.