Li R, Riordan J F, Hu G
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.
Biochem Biophys Res Commun. 1997 Sep 18;238(2):305-12. doi: 10.1006/bbrc.1997.7290.
Exogenous angiogenin undergoes rapid nuclear translocation in cultured human umbilical artery endothelial cells at 37 degrees C but not at 4 degrees C. Treatment of cells with colchicine, nocodazole and taxol, which disrupt the microtubule system, does not affect the nuclear translocation process of angiogenin, suggesting that cells transport internalized angiogenin in a microtubule independent fashion. Lysosomal inhibitors, chloroquine and leupeptin, neither inhibit nor enhance the nuclear translocation of angiogenin, indicating that lysosomal targeting and processing are not required for, and do not compete with, the nuclear translocation. Moreover, treatment of cells with a tyrosine kinase antagonist, genistein, does not change the ability of the cells to translocate angiogenin into the nucleus. We suggest that exogenous angiogenin is translocated to the nucleus by a mechanism that does not require activation of tyrosine kinase, but includes receptor-mediated endocytosis, microtubule and lysosome independent transport across the cytoplasm, and nuclear localization sequence-assisted nuclear import.
外源性血管生成素在37℃时可在培养的人脐动脉内皮细胞中迅速发生核转位，但在4℃时则不会。用秋水仙碱、诺考达唑和紫杉醇处理细胞，这些药物会破坏微管系统，但不影响血管生成素的核转位过程，这表明细胞以不依赖微管的方式转运内化的血管生成素。溶酶体抑制剂氯喹和亮抑酶肽既不抑制也不增强血管生成素的核转位，这表明溶酶体靶向和加工对于核转位不是必需的，也不与之竞争。此外，用酪氨酸激酶拮抗剂金雀异黄素处理细胞，不会改变细胞将血管生成素转运到细胞核中的能力。我们认为，外源性血管生成素通过一种不需要酪氨酸激酶激活的机制转运到细胞核，该机制包括受体介导的内吞作用、不依赖微管和溶酶体的跨细胞质转运以及核定位序列辅助的核输入。
