Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase

Endothelial monocyte activating polypeptide II (EMAPII) is a cytokine that is specifically induced by apoptosis, Its precursor (pro-EMAPII) has been s uggested to be identical to p43, which is associated with the multi-tRNA sy nthetase complex. Herein, we have demonstrated that the N-terminal domain o f pro-EMAPII interacts with the N-terminal extension of human cytoplasmic a rginyl-tRNA synthetase (RRS) using genetic and immunoprecipitation analyses . Aminoacylation activity of RRS was enhanced about 2.5-fold by the interac tion with pro-EMAPII but not with its N- or C-terminal domains alone. The N -terminal extension of RRS was not required for enzyme activity but did med iate activity stimulation by pro-EMAPII. Pro-EMAPII reduced the apparent K- m of RRS to tRNA, whereas the k(cat) value remained unchanged. Therefore, t he precursor of EMAPII is a multi-functional protein that assists aminoacyl ation in normal cells and releases the functional cytokine upon apoptosis.