Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation.

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. IMAGES:

细胞对电离辐射（ionizing radiation, IR）的应答包括诱导c-jun与早期生长应答基因1（EGR1）的表达。本研究探究了可将电离辐射诱导的信号转导至细胞核的潜在细胞质信号级联反应。实验结果显示，在人类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，与对照组相比，受照射细胞的S6肽磷酸化水平有所升高。免疫复合物激酶实验进一步证实了电离辐射诱导的pp90rsk激活。与上述结果不同的是，未检测到pp70S6K的诱导激活。既往研究已证实，丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）可激活pp90rsk。本研究结果进一步表明，电离辐射处理可诱导丝裂原活化蛋白激酶活性升高，且该事件在时间上与pp90rsk的激活及早期应答基因的表达相关。上述发现提示，丝裂原活化蛋白激酶/pp90rsk信号级联反应的激活参与了细胞对电离辐射暴露的应答过程。IMAGES: