Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation

• Published in: Neuron (Cambridge, Mass.) Vol. 21; no. 4; pp. 869 - 883
• Main Authors: Impey, S, Obrietan, K, Wong, S T, Poser, S, Yano, S, Wayman, G, Deloulme, J C, Chan, G, Storm, D R
• Format: Journal Article
• Language: English
• Published: United States 01-10-1998
• Subjects: Animals; Biological Transport - physiology; Calcium - physiology; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 4; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - physiology; Cell Nucleus - metabolism; Cyclic AMP Response Element-Binding Protein - physiology; Cyclic AMP-Dependent Protein Kinases - physiology; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Hippocampus - cytology; Hippocampus - metabolism; Long-Term Potentiation - drug effects; Neurons - physiology; PC12 Cells; Phosphorylation - drug effects; Rats; Signal Transduction - physiology; Transcription, Genetic - physiology
• ISSN: 0896-6273
• DOI: 10.1016/s0896-6273(00)80602-9

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.