Activation of a C-terminal transcriptional activation domain of ERK5 by autophosphorylation
Activation of a C-terminal transcriptional activation domain of ERK5 by autophosphorylation
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DOI：
10.1074/jbc.m704079200
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发表时间：
2007-12-07
影响因子：
4.8
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
--
作者：
Morimoto, Hiroko;Kondoh, Kunio;Nishida, Eisuke
ERK5通过调控转录在许多生物过程中起着至关重要的作用。ERK5有一个大的c端一半，其中包含一个转录激活域。然而，其转录激活活性是如何调控的尚不清楚。在这里，我们发现活化的ERK5激酶活性是c端一半增强AP-1活性所必需的，并且活化的ERK5在其最c端区域发生自磷酸化。将这些可磷酸化的苏氨酸和丝氨酸残基改变为不可磷酸化的丙氨酸显著降低ERK5的转录激活活性。此外，没有n端激酶结构域的ERK5的c端一半的拟磷突变体被证明能够增强成纤维细胞中AP-1的活性。这些结果揭示了刺激诱导的ERK5自磷酸化在基因表达调控中的作用。
ERK5 plays a crucial role in many biological processes by regulating transcription. ERK5 has a large C-terminal-half that contains a transcriptional activation domain. However, it has remained unclear how its transcriptional activation activity is regulated. Here, we show that the activated kinase activity of ERK5 is required for the C-terminal-half to enhance the AP-1 activity, and that the activated ERK5 undergoes autophosphorylation on its most C-terminal region. Changing these phosphorylatable threonine and serine residues to unphosphorylatable alanines significantly reduces the transcriptional activation activity of ERK5. Moreover, phosphomimetic mutants of the C-terminal-half of ERK5 without an N-terminal kinase domain are shown to be able to enhance the AP-1 activity in fibroblastic cells. These results reveal the role of the stimulus-induced ERK5 autophosphorylation in regulation of gene expression.