Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation
Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation
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DOI：
10.1016/s0896-6273(00)80602-9
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发表时间：
1998-10-01
期刊：
影响因子：
16.2
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Impey, S;Obrietan, K;Storm, DR
尽管Ca2+刺激的cAMP反应元件结合蛋白（CREB-）依赖转录与生长、分化和神经可塑性有关，但Ca2+激活转录的机制尚未明确。在这里，我们报告细胞外信号相关蛋白激酶（ERK）信号是Ca2+刺激的PC12细胞和海马神经元转录的必要条件。Ca2+对ERK和Rsk2的顺序激活导致CREB的磷酸化和反激活。有趣的是，Ca2+诱导的ERK和Rsk2核易位需要蛋白激酶A （PKA）激活。这可以解释为什么Ca2+刺激的creb依赖性转录需要PKA活性。此外，长期增强后期（L-LTP）和L-LTP相关的cre介导的转录的充分表达需要ERK的激活，这表明ERK对CREB的激活在持久神经元可塑性的形成中起着关键作用。
Although Ca2+-stimulated cAMP response element binding protein- (CREB-) dependent transcription has been implicated in growth, differentiation, and neuroplasticity, mechanisms for Ca2+-activated transcription have not been defined. Here, we report that extracellular signal-related protein kinase (ERK) signaling is obligatory for Ca2+-stimulated transcription in PC12 cells and hippocampal neurons. The sequential activation of ERK and Rsk2 by Ca2+ leads to the phosphorylation and transactivation of CREB. Interestingly, the Ca2+-induced nuclear translocation of ERK and Rsk2 to the nucleus requires protein kinase A (PKA) activation. This may explain why PKA activity is required for Ca2+-stimulated CREB-dependent transcription. Furthermore, the full expression of the late phase of long-term potentiation (L-LTP) and L-LTP-associated CRE-mediated transcription requires ERK activation, suggesting that the activation of CREB by ERK plays a critical role in the formation of long lasting neuronal plasticity.