Han Jung Min, Park Sang Gyu, Lee Yeonsook, Kim Sunghoon
Imagene Co. Biotechnology Incubating Center, Golden Helix, Seoul National University, Seoul 151-741, Republic of Korea.
Biochem Biophys Res Commun. 2006 Mar 31;342(1):113-8. doi: 10.1016/j.bbrc.2006.01.117. Epub 2006 Feb 2.
AIMP1 (previously known as p43) is first found as a factor associated with a macromolecular tRNA synthetase complex. However, it is also secreted and acts on diverse target cells such as endothelial cells, macrophages, and fibroblasts to control angiogenesis, inflammation, and dermal regeneration, respectively. We previously showed that AIMP1 induces the death of endothelial cell but proliferation of fibroblasts and activates macrophages. In this work, we found that elastase 2-cleaved AIMP1 retained its pro-apoptotic activity to endothelial cells but lost the growth-stimulatory activity to fibroblasts. To determine the functional domains responsible for each activity, we generated several deletion fragments of AIMP1 and compared the activities to the target cells. AIMP1 promoted endothelial cell death and caspase-3 activation through its 101-114 amino acid region, fibroblast proliferation through its 6-46 amino acid region, and endothelial migration through its 114-192 amino acid region as revealed by deletion mapping. Thus, this work revealed that AIMP1 uses different regions for its diverse extracellular activities.
AIMP1（以前称为p43）最初被发现是一种与大分子tRNA合成酶复合物相关的因子。然而，它也会分泌，并作用于多种靶细胞，如内皮细胞、巨噬细胞和成纤维细胞，分别控制血管生成、炎症和皮肤再生。我们之前表明，AIMP1诱导内皮细胞死亡，但促进成纤维细胞增殖并激活巨噬细胞。在这项研究中，我们发现弹性蛋白酶2切割后的AIMP1保留了对内皮细胞的促凋亡活性，但失去了对成纤维细胞的生长刺激活性。为了确定负责每种活性的功能结构域，我们生成了几个AIMP1的缺失片段，并比较了它们对靶细胞的活性。缺失图谱显示，AIMP1通过其101-114氨基酸区域促进内皮细胞死亡和半胱天冬酶-3激活，通过其6-46氨基酸区域促进成纤维细胞增殖，通过其114-192氨基酸区域促进内皮细胞迁移。因此，这项研究揭示了AIMP1利用不同区域发挥其多种细胞外活性。
