The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling
The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling
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DOI：
10.1074/jbc.m412599200
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发表时间：
2005-01-28
影响因子：
4.8
通讯作者：
Ullrich, A
中科院分区：
文献类型：
--
作者：
Buschbeck, M;Ullrich, A
ERK5在丝裂原活化蛋白激酶(MAPK)中是独一无二的，因为它含有一个大的C末端尾巴。我们解决了这个尾巴如何影响ERK5的信号容量的问题。C末端结构域的逐渐缺失导致ERK5激酶活性急剧增加，这依赖于上游的MAPK级联反应，从而表明尾巴可能具有自身抑制功能。有趣的是，ERK5能够自动磷酸化自己的尾巴。此外，ERK5在几乎所有类型的细胞系中都有表达，定位于细胞核和细胞质。ERK5的定位是由其C-末端结构域决定的，这些结构域也是适当的核质穿梭所必需的。综上所述，这些结果表明ERK5信号是通过其独特的C末端尾巴的存在来引导的，这可能是理解ERK5在MAPK信号转导中的关键作用的关键。
ERK5 is unique among mitogen-activated protein kinases (MAPKs) in that it contains a large C-terminal tail. We addressed the question of how this tail could affect the signaling capacity of ERK5. Gradual deletion of the C-terminal domains resulted in a drastic increase of ERK5 kinase activity, which was dependent on the upstream MAPK cascade, thus indicating a possible auto-inhibitory function of the tail. It is interesting that ERK5 was able to autophosphorylate its own tail. Moreover, ERK5, which was found to be expressed in virtually all kinds of cell lines, localized to nuclear as well as cytoplasmic compartments. The localization of ERK5 was determined by its C-terminal domains, which were also required for appropriate nucleocytoplasmic shuttling. Taken together, these results indicate that ERK5 signaling is directed by the presence of its unique C-terminal tail, which might be the key to understanding the key role of ERK5 in MAPK signaling.