Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase.
Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase.
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DOI：
10.1074/jbc.c200126200
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发表时间：
2002-06-07
影响因子：
4.8
通讯作者：
Schimmel, P
中科院分区：
文献类型：
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作者：
Wakasugi, K;Slike, BM;Schimmel, P
蛋白质合成的第一步是由氨酰-tRNA 合成酶催化的。此外，某些哺乳动物 tRNA 合成酶将蛋白质合成与细胞因子信号传导途径联系起来。特别是，人酪氨酰-tRNA合成酶（TyrRS）可以通过蛋白水解分裂成具有不同细胞因子活性的两个片段。其中一个 TyrRS 片段（微型 TyrRS）包含与 CXC 趋化因子（如白细胞介素 8）相同的特征，这些趋化因子也充当血管生成因子。此处，迷你 TyrRS（但不是全长 TyrRS）被证明可以在体外刺激内皮细胞的趋化性，并在两种体内动物模型中刺激血管生成。 mini TyrRS 的血管生成活性可被 IP-10 等抗血管生成趋化因子对抗。因此，人酪氨酰-tRNA 合成酶的生物片段将蛋白质合成与血管生成的调节联系起来。
The first step of protein synthesis is catalyzed by aminoacyl-tRNA synthetases. In addition, certain mammalian tRNA synthetases link protein synthesis to cytokine signaling pathways. In particular, human tyrosyl-tRNA synthetase (TyrRS) can be split by proteolysis into two fragments having distinct cytokine activities. One of the TyrRS fragments (mini TyrRS) contains features identical to those in CXC chemokines (like interleukin-8) that also act as angiogenic factors. Here mini TyrRS (but not full-length TyrRS) is shown to stimulate chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of two in vivo animal models. The angiogenic activity of mini TyrRS can be opposed by anti-angiogenic chemokines like IP-10. Thus, a biological fragment of human tyrosyl-tRNA synthetase links protein synthesis to regulation of angiogenesis.