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首页> 外文期刊>Cellular Signalling >The duration of ERK 1/2 activity determines the activation of c-Fos and Fra-1 and the composition and quantitative transcriptional output of AP-1
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The duration of ERK 1/2 activity determines the activation of c-Fos and Fra-1 and the composition and quantitative transcriptional output of AP-1

机译：ERK 1/2活性的持续时间决定了c-Fos和Fra-1的激活以及AP-1的组成和定量转录输出

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The duration of ERK 1/2 activation influences the nature of the biological response to agonist. Members of the AP-1 transcription factor family are well known targets of the ERK1/2 pathway and are expressed in a temporally coordinated fashion during cell cycle re-entry. In CC139 fibroblasts, sustained ERK1/2 activation is required for the expression of Fra-1, Fra-2, c-Jun and JunB, whereas expression of c-Fos is still strongly induced even in response to transient ERK activation. However, the significance of this pattern of expression for AP-1 activity has not been addressed. Here we show that growth factor stimulated activation of the C-terminal c-Fos transactivation domain (TAD) serves as a sensor for ERK1/2 signal duration whereas the c-JunTAD is not responsive to growth factors. In addition, sustained ERK1/2 activation determines the duration of increases in AP-1 DNA binding complexes as well as their qualitative make up. Finally, this is reflected in both the duration and quantitative transcriptional output of stably integrated AP-1 reporter constructs, indicating that AP-1 activity is finely tuned to ERK1/2 signal duration. These results provide new insights into the importance of ERK 1/2 signal duration in the regulation of AP-1 and provide an explanation for how differences in signal duration can lead to both quantitative and qualitative changes in gene expression. (c) 2006 Elsevier Inc. All rights reserved.
机译：ERK 1/2激活的持续时间影响对激动剂的生物学反应的性质。 AP-1转录因子家族的成员是ERK1 / 2途径的众所周知的靶标，并且在细胞周期再进入过程中以时间协调的方式表达。在CC139成纤维细胞中，表达Fra-1，Fra-2，c-Jun和JunB需要持续的ERK1 / 2激活，而即使响应短暂的ERK激活，仍强烈诱导c-Fos的表达。但是，这种表达方式对AP-1活性的重要性尚未得到解决。在这里，我们显示生长因子刺激的C端c-Fos反式激活域（TAD）的激活充当ERK1 / 2信号持续时间的传感器，而c-JunTAD对生长因子没有响应。此外，持续的ERK1 / 2激活决定了AP-1 DNA结合复合物增加的持续时间及其定性组成。最后，这在稳定整合的AP-1报告基因构建体的持续时间和定量转录输出中均得到反映，表明AP-1活性已微调至ERK1 / 2信号持续时间。这些结果为ERK 1/2信号持续时间在调节AP-1中的重要性提供了新的见解，并为信号持续时间的差异如何导致基因表达的定量和定性变化提供了解释。 （c）2006 Elsevier Inc.保留所有权利。

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