Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase
Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase
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DOI：
10.1074/jbc.274.24.16673
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发表时间：
1999-06-11
影响因子：
4.8
通讯作者：
Shiba, K
中科院分区：
文献类型：
--
作者：
Park, SG;Jung, KH;Shiba, K
内皮单核细胞激活多肽 II (EMAAPII) 是一种由细胞凋亡特异性诱导的细胞因子，其前体 (pro-EMAAPII) 被认为与 p43 相同，p43 与多 tRNA 合成酶复合物相关。在此，我们通过遗传和免疫沉淀分析证明了 pro-EMAPII 的 N 端结构域与人细胞质精氨酰-tRNA 合成酶 (RRS) 的 N 端延伸相互作用。通过与 pro-EMAPII 相互作用，RRS 的氨酰化活性增强了约 2.5 倍，但仅与其 N 端或 C 端结构域相互作用时，RRS 的氨酰化活性增强了约 2.5 倍。 RRS 的 N 末端延伸不是酶活性所必需的，但确实介导 pro-EMAPII 的活性刺激。 Pro-EMAPII 降低了 RRS 与 tRNA 的表观 K-m，而 k(cat) 值保持不变。因此，EMAPII的前体是一种多功能蛋白，可协助正常细胞中的氨酰化并在细胞凋亡时释放功能性细胞因子。
Endothelial monocyte activating polypeptide II (EMAPII) is a cytokine that is specifically induced by apoptosis, Its precursor (pro-EMAPII) has been suggested to be identical to p43, which is associated with the multi-tRNA synthetase complex. Herein, we have demonstrated that the N-terminal domain of pro-EMAPII interacts with the N-terminal extension of human cytoplasmic arginyl-tRNA synthetase (RRS) using genetic and immunoprecipitation analyses. Aminoacylation activity of RRS was enhanced about 2.5-fold by the interaction 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 mediate activity stimulation by pro-EMAPII. Pro-EMAPII reduced the apparent K-m of RRS to tRNA, whereas the k(cat) value remained unchanged. Therefore, the precursor of EMAPII is a multi-functional protein that assists aminoacylation in normal cells and releases the functional cytokine upon apoptosis.