Kharbanda S, Saleem A, Shafman T, Emoto Y, Weichselbaum R, Kufe D
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5416-20. doi: 10.1073/pnas.91.12.5416.
The cellular response to ionizing radiation (IR) includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. The results demonstrate activation of the 40S ribosomal protein S6 kinase, pp90rsk, in human U-937 myeloid leukemia cells. Partial purification of pp90rsk by affinity chromatography demonstrated an increase in S6 peptide phosphorylation when comparing irradiated with control cells. IR-induced activation of pp90rsk was further confirmed in immune-complex kinase assays. In contrast to these findings, there was no detectable induction of pp70S6K. Previous work has demonstrated that mitogen-activated protein kinase activates pp90rsk. The present results further show that IR treatment is associated with induction of mitogen-activated protein kinase activity and that this event is temporally related to activation of pp90rsk and early response gene expression. These findings suggest that activation of the mitogen-activated protein kinase/pp90rsk cascade is involved in the response of cells to IR exposure.
细胞对电离辐射（IR）的反应包括诱导c-jun和EGR1早期反应基因。目前的研究工作检测了将IR诱导信号转导至细胞核的潜在细胞质信号级联反应。结果表明，在人U-937髓系白血病细胞中，40S核糖体蛋白S6激酶pp90rsk被激活。通过亲和层析对pp90rsk进行部分纯化后发现，与对照细胞相比，照射后的细胞中S6肽的磷酸化增加。在免疫复合物激酶分析中进一步证实了IR诱导的pp90rsk激活。与这些发现相反，未检测到pp70S6K的诱导。先前的研究表明，丝裂原活化蛋白激酶可激活pp90rsk。目前的结果进一步表明，IR处理与丝裂原活化蛋白激酶活性的诱导有关，并且这一事件在时间上与pp90rsk的激活和早期反应基因的表达相关。这些发现表明，丝裂原活化蛋白激酶/pp90rsk级联反应的激活参与了细胞对IR暴露的反应。
