Rowley Matt, Van Ness Brian
Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, The University of Minnesota, Minneapolis, Minnesota, MN 55455, USA.
Oncogene. 2002 Dec 12;21(57):8769-75. doi: 10.1038/sj.onc.1205387.
Ras is a major signaling molecule activated by interleukin-6. There have been no published reports, however, that specifically examine the kinetics and percentage of Ras activation in response to IL-6. Model cell lines were used to study activation of N- and K-ras induced by IL-6. All of the myeloma cell lines we tested express both N-ras and K-ras, but not H-ras. GTP-bound Ras was measured and the percentage of the total Ras pool that was activated in response to IL-6 was calculated. IL-6 is able to transiently activate both N- and K-ras in the ANBL6 cell line. In addition, increasing concentrations of IL-6 are able to activate increasing levels of both N- and K-ras. One ng/ml of IL-6 is able to activate approximately 10% of the N-ras pool and 18% of the K-ras pool. The amount of Ras-GTP in the cells correlates with the level of proliferation at low levels, but proliferation plateaus when higher levels of Ras-GTP are present. Protection from dexamethasone-induced apoptosis correlates with IL-6 concentration and Ras activation. However, IL-6 enhances apoptosis induced by doxorubicin. Interestingly, the ANBL6 cell line transfected with an N-ras12 or a K-ras12 gene is protected from doxorubicin-induced apoptosis.
Ras是一种由白细胞介素-6激活的主要信号分子。然而，尚无专门研究Ras对白细胞介素-6反应的动力学和激活百分比的已发表报告。使用模型细胞系研究白细胞介素-6诱导的N-Ras和K-Ras激活。我们测试的所有骨髓瘤细胞系均表达N-Ras和K-Ras，但不表达H-Ras。测量结合GTP的Ras，并计算响应白细胞介素-6激活的总Ras库的百分比。白细胞介素-6能够在ANBL6细胞系中瞬时激活N-Ras和K-Ras。此外，白细胞介素-6浓度的增加能够激活更高水平的N-Ras和K-Ras。1 ng/ml的白细胞介素-6能够激活约10%的N-Ras库和18%的K-Ras库。细胞中Ras-GTP的量在低水平时与增殖水平相关，但当存在较高水平的Ras-GTP时增殖达到平台期。对地塞米松诱导的细胞凋亡的保护作用与白细胞介素-6浓度和Ras激活相关。然而，白细胞介素-6增强阿霉素诱导的细胞凋亡。有趣的是，用N-Ras12或K-Ras12基因转染的ANBL6细胞系对阿霉素诱导的细胞凋亡具有抗性。
