Raingeaud J, Whitmarsh A J, Barrett T, Dérijard B, Davis R J
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605 USA.
Mol Cell Biol. 1996 Mar;16(3):1247-55. doi: 10.1128/MCB.16.3.1247.
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway.
p38丝裂原活化蛋白(MAP)激酶信号转导通路可被促炎细胞因子和环境应激激活。在活化细胞的细胞核中检测到p38 MAP激酶,这表明p38 MAP激酶可介导向细胞核的信号传导。为了验证这一假设,我们构建了活化型MKK3和MKK6的表达载体,这两种MAP激酶激酶可磷酸化并激活p38 MAP激酶。活化型MKK3和MKK6在培养细胞中的表达导致p38 MAP激酶活性选择性增加。共转染实验表明,p38 MAP激酶激活导致由转录因子ATF2和Elk-1介导的报告基因表达增加。这些数据表明,细胞核是p38 MAP激酶信号转导通路的一个靶点。