In vivo expression and regulation of Elk-1, a target of the extracellular-regulated kinase signaling pathway, in the adult rat brain.
The transcription factor Elk-1, a nuclear target of extracellular-regulated kinases (ERKs), plays a pivotal role in immediate early gene induction by external stimuli. Notably, the degree of phosphorylation of Elk-1 is tightly correlated with the level of activation of transcription of c-fos by proliferative signals. No data yet indicate the role of Elk-1 in the adult brain in vivo. To address this question, we have analyzed in the present work (1) Elk-1 mRNA and protein expression in the adult rat brain, and (2) the regulation of Elk-1 (i.e., its phosphorylation state) in an in vivo model of immediate early gene (IEG) induction: an electrical stimulation of the cerebral cortex leading to c-fos and zif268 mRNA induction in the striatum. Using in situ hybridization, we show that Elk-1 mRNA is expressed in various brain structures of adult rat, and that this expression is exclusively neuronal. We demonstrate by immunocytochemistry using various specific Elk-1 antisera that the protein is not only nuclear (as shown previously in transiently transfected cell lines) but is also present in soma, dendrites, and axon terminals. On electrical stimulation of the glutamatergic corticostriatal pathway, we show a strict spatiotemporal correspondence among ERK activation, Elk-1 phosphorylation, and IEG mRNA induction. Furthermore, both activated proteins, analyzed by immunocytochemistry, are found in cytosolic and nuclear comparments of neuronal cells in the activated area. Our data suggest that the ERK signaling pathway plays an important role in regulating genes controlled by serum response element sites via phosphorylation of Elk-1 in vivo.
Sgambato
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Laboratoire de Neurochimie-Anatomie, Institut des Neurosciences-Unité de Recherche Associée 1488, Université Pierre et Marie Curie, 75005 Paris, France.
Vanhoutte
P
P
Pagès
C
C
Rogard
M
M
Hipskind
R
R
Besson
M J
MJ
Caboche
J
J
D000209:Acute-Phase Proteins / Q000032:analysis; D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry; D002540:Cerebral Cortex / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D051766:Early Growth Response Protein 1; D005110:Extracellular Space / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000235:genetics; D050807:ets-Domain Protein Elk-1
D000209:Acute-Phase Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C494114:Elk1 protein, rat; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium