Corticotropin-releasing factor and vasoactive intestinal polypeptide activate gene transcription through the cAMP signaling pathway in a catecholaminergic immortalized neuron.
Corticotropin-releasing factor (CRF) and vasoactive intestinal polypeptide (VIP) are neuropeptides displaying a variety of short-term effects in the nervous system. It is shown here in transfection experiments of an immortalized noradrenergic locus coeruleus-like cell line that both CRF and VIP also trigger a signaling cascade capable of activating gene transcription. To elucidate the signaling pathway leading to transcriptional induction, cells were transfected with an inhibitor for cAMP-dependent protein kinase, targeted to the nucleus via a nuclear-localization signal. Transcriptional induction of a reporter gene by CRF and VIP was blocked in these cells, indicating that the cAMP-dependent protein kinase is required for transducing CRF and VIP generated signals into the nucleus. Additionally, transfection experiments with a reporter gene containing cAMP response elements in its regulatory region demonstrate that CRF and VIP receptor activation induce transcription through this genetic regulatory element. We conclude that long-term effects of CRF and VIP in neurons are likely to be mediated by the transcriptional regulation of CRF and VIP-responsive genes via the cAMP signaling pathway.
Thiel
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Medical Biochemistry and Molecular Biology, University of the Saarland, Medical School, Homburg, Germany. bcgthi@med-rz.uni-sb.de
Cibelli
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D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000201:enzymology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D014660:Vasoactive Intestinal Peptide; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine