Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms
Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms
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DOI：
10.1128/mcb.26.5.1679-1690.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Kondoh, K;Terasawa, K;Nishida, E
细胞外信号调节激酶 5 (ERK5) 是丝裂原激活蛋白激酶家族的成员，在细胞核的生长因子信号传导中发挥着重要作用。然而，调节 ERK5 亚细胞定位的分子机制仍不清楚。在这里，我们发现 ERK5 的核质穿梭受到二分核定位信号依赖的核输入机制和 CRM1 依赖的核输出机制的调节。我们的结果表明，ERK5 的 N 端一半与 C 端一半结合，并且这种结合对于 ERK5 的核输出是必需的。他们进一步表明，MEK5 激活 ERK5 磷酸化导致 N 端和 C 端半部之间的结合解离，从而抑制 ERK5 的核输出，导致其核输入。这些结果揭示了 ERK5 的激活磷酸化诱导其核输入的机制，并提出了蛋白质核质穿梭的磷酸化依赖性控制机制的新例子。
Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase family, plays an important role in growth factor signaling to the nucleus. However, molecular mechanisms regulating subcellular localization of ERK5 have remained unclear. Here, we show that nucleocytoplasmic shuttling of ERK5 is regulated by a bipartite nuclear localization signal-dependent nuclear import mechanism and a CRM1-dependent nuclear export mechanism. Our results show that the N-terminal half of ERK5 binds to the C-terminal half and that this binding is necessary for nuclear export of ERK5. They further show that the activating phosphorylation of ERK5 by MEK5 results in the dissociation of the binding between the N- and C-terminal halves and thus inhibits nuclear export of ERK5, causing its nuclear import. These results reveal the mechanism by which the activating phosphorylation of ERK5 induces its nuclear import and suggest a novel example of a phosphorylation-dependent control mechanism for nucleocytoplasmic shuttling of proteins.