Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology
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Animals
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Cell Nucleus / metabolism
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Cell Nucleus / ultrastructure
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Conditioning, Psychological / physiology*
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Cyclic AMP / analogs & derivatives*
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cytoplasm / metabolism
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Cytoplasm / ultrastructure
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DNA-Binding Proteins*
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Fear / physiology*
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Hippocampus / cytology
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Hippocampus / metabolism*
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Immunohistochemistry
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Learning / physiology*
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MAP Kinase Signaling System / physiology
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Male
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Mice
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases / metabolism*
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Mossy Fibers, Hippocampal / metabolism
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Mossy Fibers, Hippocampal / ultrastructure
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Phosphorylation
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Proto-Oncogene Proteins / metabolism*
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Pyramidal Cells / cytology
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Pyramidal Cells / metabolism
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
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Thionucleotides / pharmacology
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Transcription Factors*
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Up-Regulation / physiology
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ets-Domain Protein Elk-1
Substances
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DNA-Binding Proteins
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Elk1 protein, mouse
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Proto-Oncogene Proteins
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Thionucleotides
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Transcription Factors
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ets-Domain Protein Elk-1
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adenosine-3',5'-cyclic phosphorothioate
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Adenosine Triphosphate
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Cyclic AMP
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Ribosomal Protein S6 Kinases, 90-kDa
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases