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

Neuron. 1998 Oct;21(4):869-83. doi: 10.1016/s0896-6273(00)80602-9.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Flavonoids
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Camk4 protein, rat
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Calcium