Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Transport / physiology
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Calcium / physiology*
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Calcium Signaling
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cell Nucleus / metabolism*
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Cyclic AMP Response Element-Binding Protein / physiology*
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Cyclic AMP-Dependent Protein Kinases / physiology*
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Hippocampus / cytology
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Hippocampus / metabolism
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Long-Term Potentiation / drug effects
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Neurons / physiology
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PC12 Cells
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Phosphorylation / drug effects
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Rats
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Signal Transduction / physiology
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Transcription, Genetic / physiology*
Substances
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Flavonoids
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Cyclic AMP-Dependent Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, rat
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Calcium