Phosphorylation of hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during contextual fear conditioning: interactions between Erk-1/2 and Elk-1

Mol Cell Neurosci. 2002 Nov;21(3):463-76. doi: 10.1006/mcne.2002.1188.


The phosphorylation of proteins involved in the MAP kinase signal transduction pathway was investigated during associative learning of C57BL/6J mice. Context-dependent fear conditioning, consisting of a single exposure of mice to a context followed by foot shock, was employed as a learning paradigm. Control groups consisted of mice exposed to context only or an immediate shock in the context. Coincident up-regulation of phosphorylated Erk-1/2 and Elk-1 was observed in the CA3 hippocampal subfield and dentate gyrus 30 min after fear conditioning but not after the control paradigms. Phosphorylated Erk-1/2 and Elk-1 were associated and predominantly colocalized in the mossy fibers. In vitro kinase assays showed that hippocampal Erk-1/2 phosphorylates Elk-1. Notably, Elk-1 in turn enhances the phosphorylation of Erk-1/2 and its downstream target p90Rsk-1. Increased phosphorylation and nuclear translocation of p90Rsk-1 was also demonstrated in the CA3 hippocampal area in vivo during contextual fear conditioning. The observed interactions between hippocampal Elk-1 and Erk-1/2 proteins may affect the consolidation of contextual memories through activation of the downstream nuclear targets of Erk-1/2, such as p90Rsk-1, without requiring nuclear translocation of Elk-1 and Erk-1/2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Conditioning, Psychological / physiology*
  • Cyclic AMP / analogs & derivatives*
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoplasm / metabolism
  • Cytoplasm / ultrastructure
  • DNA-Binding Proteins*
  • Fear / physiology*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Learning / physiology*
  • MAP Kinase Signaling System / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mossy Fibers, Hippocampal / metabolism
  • Mossy Fibers, Hippocampal / ultrastructure
  • Phosphorylation
  • Proto-Oncogene Proteins / metabolism*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Thionucleotides / pharmacology
  • Transcription Factors*
  • Up-Regulation / physiology
  • ets-Domain Protein Elk-1


  • DNA-Binding Proteins
  • Elk1 protein, mouse
  • Proto-Oncogene Proteins
  • Thionucleotides
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • adenosine-3',5'-cyclic phosphorothioate
  • Adenosine Triphosphate
  • Cyclic AMP
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases