Two distinct cytokines released from a human aminoacyl-tRNA synthetase

Two distinct cytokines released from a human aminoacyl-tRNA synthetase
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DOI:
10.1126/science.284.5411.147
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发表时间:
1999-04-02
期刊:
影响因子:
56.9
通讯作者:
Schimmel, P
Schimmel, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wakasugi, K;Schimmel, P

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氨酰-tRNA合成酶催化转移RNA(tRNA)的氨酰化。人酪氨酰-tRNA合成酶可分裂成两个具有不同细胞因子活性的片段。内皮单核细胞激活多肽II样羧基末端结构域具有强的白细胞和单核细胞趋化活性,并刺激髓过氧化物酶、肿瘤坏死因子-α和组织因子的产生。催化性氨基末端结构域与白细胞介素-8 A型受体结合,并作为白细胞介素-8样细胞因子发挥作用。在细胞培养中的凋亡条件下,全长酶被分泌,并且两种细胞因子活性可以由白细胞弹性蛋白酶(一种细胞外蛋白酶)产生。这种tRNA合成酶的分泌可能通过阻止翻译和产生所需的细胞因子来促进细胞凋亡。
Aminoacyl-tRNA synthetases catalyze aminoacylation of transfer RNAs (tRNAs). It is shown that human tyrosyl-tRNA synthetase can be split into two fragments with distinct cytokine activities, The endothelial monocyte-activating polypeptide Ii-Like carboxy-terminal domain has potent leukocyte and monocyte chemotaxis activity and stimulates production of myeloperoxidase, tumor necrosis factor-alpha, and tissue factor. The catalytic amino-terminal domain binds to the interleukin-8 type A receptor and functions as an interleukin-8-like cytokine. Under apoptotic conditions in cell culture, the full-length enzyme is secreted, and the two cytokine activities can be generated by Leukocyte elastase, an extracellular protease. Secretion of this tRNA synthetase may contribute to apoptosis both by arresting translation and producing needed cytokines.