Phosphorylation of Hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during Contextual Fear Conditioning: Interactions between Erk-1/2 and Elk-1
Phosphorylation of Hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during Contextual Fear Conditioning: Interactions between Erk-1/2 and Elk-1
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DOI：
10.1006/mcne.2002.1188
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发表时间：
2002-11
影响因子：
3.5
通讯作者：
F. Sananbenesi;A. Fischer;Christina Schrick;J. Spiess;J. Radulovic
中科院分区：
文献类型：
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作者：
F. Sananbenesi;A. Fischer;Christina Schrick;J. Spiess;J. Radulovic
研究了C57 BL/6 J小鼠在联想学习过程中MAP激酶信号转导通路中蛋白质的磷酸化。上下文依赖的恐惧条件反射，包括一个单一的曝光的小鼠的背景下，然后用脚电击，作为一个学习范例。对照组由仅暴露于环境或在环境中立即休克的小鼠组成。同时上调磷酸化的Erk-1/2和Elk-1观察到在CA 3海马子区和齿状回恐惧条件化后30分钟，但没有后控制范式。磷酸化的Erk-1/2和Elk-1相关联，并主要共定位在苔藓纤维。体外激酶测定表明，海马Erk-1/2磷酸化Elk-1。值得注意的是，Elk-1反过来增强Erk-1/2及其下游靶点p90 Rsk-1的磷酸化。增加磷酸化和核转位的p90 Rsk-1也证明在海马CA 3区在体内的上下文恐惧条件反射。所观察到的海马Elk-1和Erk-1/2蛋白之间的相互作用可能通过激活Erk-1/2的下游核靶点（如p90 Rsk-1）而影响背景记忆的巩固，而不需要Elk-1和Erk-1/2的核转位。
The phosphorylation of proteins involved in the MAP kinase signal transduction pathway was investigated during associative learning of C57BL/6J mice. Context-dependent fear conditioning, consisting of a single exposure of mice to a context followed by foot shock, was employed as a learning paradigm. Control groups consisted of mice exposed to context only or an immediate shock in the context. Coincident up-regulation of phosphorylated Erk-1/2 and Elk-1 was observed in the CA3 hippocampal subfield and dentate gyrus 30 min after fear conditioning but not after the control paradigms. Phosphorylated Erk-1/2 and Elk-1 were associated and predominantly colocalized in the mossy fibers. In vitro kinase assays showed that hippocampal Erk-1/2 phosphorylates Elk-1. Notably, Elk-1 in turn enhances the phosphorylation of Erk-1/2 and its downstream target p90Rsk-1. Increased phosphorylation and nuclear translocation of p90Rsk-1 was also demonstrated in the CA3 hippocampal area in vivo during contextual fear conditioning. The observed interactions between hippocampal Elk-1 and Erk-1/2 proteins may affect the consolidation of contextual memories through activation of the downstream nuclear targets of Erk-1/2, such as p90Rsk-1, without requiring nuclear translocation of Elk-1 and Erk-1/2.