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Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular
E Valjent1, J Caboche, P Vanhoutte
1Laboratoire de Signalisation Neuronale et Régulations Géniques, CNRS-Université Pierre et Marie Curie, Paris, France.
Abstract:
The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling cascade involved in a plethora of physiological responses, including cell proliferation, survival, differentiation, and, in neuronal cells, synaptic plasticity. Increasing evidence now implicates this pathway in cognitive functions, such as learning and memory formation, and also in behavioral responses to addictive drugs. Although multiple intracellular substrates can be activated by ERKs, nuclear targeting of transcription factors, and thereby control of gene expression, seems to be a major event in ERK-induced neuronal adaptation. By controlling a prime burst of gene expression, ERK signaling could be critically involved in molecular adaptations that are necessary for long-term behavioral changes. Reviewed here are data providing evidence for a role of ERKs in long-term behavioral alterations, and the authors discuss molecular mechanisms that could underlie this role.
Insights
The extracellular signal-regulated kinase (ERK) pathway influences learning, memory, and drug responses. ERK signaling controls gene expression, enabling long-term behavioral changes and neuronal adaptation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway is a conserved signaling cascade.
- ERK pathway activation is crucial for physiological processes like cell proliferation, survival, differentiation, and synaptic plasticity in neurons.
Purpose of the Study:
- To review evidence for the role of ERKs in long-term behavioral alterations.
- To discuss the molecular mechanisms underlying ERK involvement in neuronal adaptation and behavior.
Main Methods:
- Literature review of existing research on ERK signaling.
- Analysis of data linking ERK pathway to cognitive functions and drug responses.
- Discussion of molecular mechanisms, including transcription factor nuclear targeting.
Main Results:
- ERK pathway is implicated in cognitive functions such as learning and memory.
- ERK signaling plays a role in behavioral responses to addictive drugs.
- Nuclear translocation of transcription factors, regulated by ERKs, is a key event in neuronal adaptation.
Conclusions:
- ERK signaling is critically involved in molecular adaptations necessary for long-term behavioral changes.
- Understanding ERK-mediated gene expression provides insight into long-term behavioral modifications.
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