Molecular Neurobiology

, Volume 23, Issue 2–3, pp 83–99

Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain

A molecular substrate for learning and memory?
  • Emmanuel Valjent
  • Jocelyne Caboche
  • Peter Vanhoutte
Article

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.

Index Entries

MAPK/ERK long-term memory MEK inhibitors synaptic plasticity gene regulation 

Abbreviations

AT

after training

BT

before training

CamK

calcium/calmodulin-dependent kinase

CBP

CREB-binding protein

CRE

cAMP and calcium-responsive element

CREB

cAMP and calcium-responsive element binding protein

ERK

extracellular signal-regulated kinase

GEF

guanine nucleotide exchange factor

GPCR

G-protein-coupled receptor

IEG

immediate-early gene

JNK

c-Jun N-terminal kinase

LTM

long-term memory

LTP

long-term potentiation

MAPK

mitogen-activated protein kinase

MEK

MAPK/ERK kinase

PKA

cAMP-dependant kinase

Ras-GRF

Ras guanine-nucleotide releasing factor

RSK2

Ribosomal S6 kinase 2

SRE

serum response element

SRF

serum response factor

STM

short-term memory

TCF

ternary complex factor

VSCC

voltage-sensitive calcium channel

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Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Emmanuel Valjent
    • 1
  • Jocelyne Caboche
    • 1
  • Peter Vanhoutte
    • 1
  1. 1.Laboratoire de Signalisation Neuronale et Régulations GéniquesCNRS-Université Pierre et Marie CurieParisFrance

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