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| http://purl.uniprot.org/citations/21948387 | http://www.w3.org/2000/01/rdf-schema#comment | "The neurosteroid pregnenolone sulfate activates a signaling cascade in insulinoma cells involving activation of extracellular signal-regulated protein kinase and enhanced expression of the transcription factor Egr-1. Here, we show that pregnenolone sulfate stimulation leads to a significant elevation of activator protein-1 (AP-1) activity in insulinoma cells. Expression of the basic region leucine zipper (bZIP) transcription factors c-Jun and c-Fos is up-regulated in insulinoma cells and pancreatic β-cells in primary culture after pregnenolone sulfate stimulation. Up-regulation of a chromatin-embedded c-Jun promoter/luciferase reporter gene transcription in pregnenolone sulfate-stimulated insulinoma cells was impaired when the AP-1 binding sites were mutated, indicating that these motifs function as pregnenolone sulfate response elements. In addition, phosphorylation of cAMP response element (CRE)-binding protein is induced and transcription of a CRE-controlled reporter gene is stimulated after pregnenolone sulfate treatment, indicating that the CRE functions as a pregnenolone sulfate response element as well. Pharmacological and genetic experiments revealed that both L-type Ca(2+) channels and transient receptor potential melastatin 3 (TRPM3) channels are essential for connecting pregnenolone sulfate stimulation with enhanced AP-1 activity and bZIP-mediated transcription in insulinoma cells. In contrast, pregnenolone sulfate stimulation did not enhance AP-1 activity or c-Jun and c-Fos expression in pituitary corticotrophs that express functional L-type Ca(2+) channels but only trace amounts of TRPM3. We conclude that expression of L-type Ca(2+) channels is not sufficient to activate bZIP-mediated gene transcription by pregnenolone sulfate. Rather, additional expression of TRPM3 or depolarization of the cells is required to connect pregnenolone sulfate stimulation with enhanced gene transcription."xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.111.074781"xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/author | "Thiel G."xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/author | "Muller I."xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/author | "Rossler O.G."xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/name | "Mol Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/pages | "1179-1189"xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/title | "Pregnenolone sulfate activates basic region leucine zipper transcription factors in insulinoma cells: role of voltage-gated Ca2+ channels and transient receptor potential melastatin 3 channels."xsd:string |
| http://purl.uniprot.org/citations/21948387 | http://purl.uniprot.org/core/volume | "80"xsd:string |
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