MAPK regulation of gene expression in the central nervous system

MAPK regulation of gene expression in the central nervous system
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DOI:
10.55782/ane-2000-1357
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发表时间:
2000-01-01
影响因子:
1.4
通讯作者:
Sweatt, JD
Sweatt, JD
中科院分区:
医学4区
文献类型:
--
作者:
Adams, JP;Roberson, ED;Sweatt, JD

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长时程增强(LTP)是一种长期记忆的细胞模型,通常被认为由依赖自主蛋白激酶活性的短期阶段和依赖基因表达和新蛋白质合成变化的长期阶段组成。同样,长期记忆表现出对基因表达和蛋白质合成改变的依赖。最近的证据表明丝裂原激活蛋白激酶 (MAPK) 级联在 LTP 和长期记忆中发挥作用。迄今为止,MAPK级联主要是在细胞分裂和增殖的背景下研究的,因此,MAPK级联调节基因表达的机制受到了相当多的关注。鉴于 LTP 后期和长期记忆中基因表达改变的可能作用,我们评估了 MAPK ERK(细胞外信号调节激酶)调节海马 CA1 区转录因子 cAMP 反应元件结合蛋白 (CREB) 磷酸化的能力。我们的研究表明 MAPK 级联在海马 CREB ​​磷酸化调节中发挥着关键作用。
Long-term potentiation (LTP), a cellular model for long-term memory, is generally acknowledged to consist of both a short-term phase that is characterized by a dependence on autonomous protein kinase activity, and a long-term phase that is characterized by a dependence on changes in gene expression and new protein synthesis. Similarly, long-term memory exhibits a dependence on gene expression and altered protein synthesis. Recent evidence indicates that the mitogen-activated protein kinase (MAPK) cascade plays a role in both LTP and long-term memory. The MAPK cascade has heretofore largely been studied in the context of cell division and proliferation and as such, mechanisms for the regulation of gene expression by the MAPK cascade have received considerable attention. Given the possible role of altered gene expression in the late phase of LTP and in long-term memory, we evaluated the capacity of the MAPK ERK (extracellular signal-regulated kinase) to regulate phosphorylation of the transcription factor cAMP response element binding protein (CREB) in hippocampal area CA1. Our studies indicate a critical role for the MAPK cascade in the regulation of CREB phosphorylation in the hippocampus.