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Synergistic induction of neurotensin gene transcription in PC12 cells parallels changes in AP-1 activity.

Authors: Bullock, BP  McNeil, GP  Dobner, PR 
Citation: Bullock BP, etal., Brain Res Mol Brain Res. 1994 Dec;27(2):232-42.
Pubmed: (View Article at PubMed) PMID:7898306

A consensus AP-1 site in the promoter of the rat neurotensin/neuromedin N (NT/N) gene is a critical regulatory element required for synergistic regulation by combinations of nerve growth factor (NGF), lithium, glucocorticoids, and adenylate cyclase activators. A rapid RNase protection assay was developed to examine the kinetics of NT/N gene activation and to determine whether activation requires newly synthesized proteins. Either NGF or lithium in combination with dexamethasone and forskolin transiently activated NT/N gene expression, but with distinct kinetics. Protein synthesis was not required for activation when NGF was used as the permissive inducer, but was required for the rapid down-regulation of the response. In contrast, lithium responses were attenuated in the absence of protein synthesis, consistent with a requirement for newly synthesized AP-1 complexes in activation. In all cases, increases in NT/N gene expression closely paralleled increases in AP-1 binding activity. Lithium in combination with other inducers caused delayed increases in both AP-1 binding activity and c-jun, c-fos and fra-1 gene expression. These results indicate that NGF and lithium exert their effects on NT/N gene expression through distinct pathways. The lithium pathway is active in neuronally-differentiated PC12 cells and could potentially be involved in the regulation of NT/N gene expression in the nervous system.


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CRRD Object Information
CRRD ID: 9743905
Created: 2015-02-19
Species: All species
Last Modified: 2015-02-19
Status: ACTIVE


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