Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation
1998; Cell Press; Volume: 21; Issue: 4 Linguagem: Inglês
10.1016/s0896-6273(00)80602-9
ISSN1097-4199
AutoresSoren Impey, Karl Obrietan, Scott T. Wong, Steven Poser, Shigetoshi Yano, Gary A. Wayman, Jean-Christophe Deloulme, Guy C.‐K. Chan, Daniel R. Storm,
Tópico(s)Melanoma and MAPK Pathways
ResumoAbstract Although Ca 2+ -stimulated cAMP response element binding protein– (CREB-) dependent transcription has been implicated in growth, differentiation, and neuroplasticity, mechanisms for Ca 2+ -activated transcription have not been defined. Here, we report that extracellular signal–related protein kinase (ERK) signaling is obligatory for Ca 2+ -stimulated transcription in PC12 cells and hippocampal neurons. The sequential activation of ERK and Rsk2 by Ca 2+ leads to the phosphorylation and transactivation of CREB. Interestingly, the Ca 2+ -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 Ca 2+ -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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