TY - JOUR
T1 - Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation
AU - Impey, Soren
AU - Obrietan, Karl
AU - Wong, Scott T.
AU - Poser, Steve
AU - Yano, Shigetoshi
AU - Wayman, Gary
AU - Deloulme, Jean Christophe
AU - Chan, Guy
AU - Storm, Daniel R.
N1 - Funding Information:
We thank Ed Krebs for the MEK mutants, Tom Soderling for CaMKIV constructs, Marc Montminy for Gal4–CREB constructs, Richard Goodman for KCREB, Silvio Gutkind for the Ras QL plasmid, Neil Nathanson for the Ras QL construct, and Randy Moon for the dominant negative PKA-GFP. We thank Dr. Zhengui Xia for discussions and critical reading of the manuscript. Microscopy and image analysis was conducted in the W. M. Keck Center for Neural Signaling at the University of Washington. This research was supported by National Institutes of Health grant NS 20498.
PY - 1998/10
Y1 - 1998/10
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(00)80602-9
DO - 10.1016/S0896-6273(00)80602-9
M3 - Article
C2 - 9808472
AN - SCOPUS:0032191933
SN - 0896-6273
VL - 21
SP - 869
EP - 883
JO - Neuron
JF - Neuron
IS - 4
ER -