Protein kinase activity-dependent inhibition of urokinase-type plasminogen activator gene transcription by cyclic AMP in human pre-B lymphoma cell line RC-K8
| Autor: | Ko-ichi Hiraga, Masahiro Shinbo, Maher Al-mokdad, Yumiko Hayakawa, Kenji Niiya, Nobuo Sakuragawa, Masao Fujimaki |
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| Rok vydání: | 1995 |
| Předmět: |
Transcription
Genetic Pre-B lymphoma cell line Cycloheximide Biology chemistry.chemical_compound Gene expression Protein biosynthesis Cyclic AMP Tumor Cells Cultured Humans Northern blot RNA Messenger Alprostadil Protein kinase A Molecular Biology Regulation of gene expression cAMP-dependent protein kinase Urokinase-type plasminogen activator (uPA) Cell Biology Molecular biology Cyclic AMP-Dependent Protein Kinases Urokinase-Type Plasminogen Activator Recombinant Proteins Enzyme Activation chemistry Bucladesine Gene Expression Regulation Cell culture Culture Media Conditioned Plasminogen activator |
| Zdroj: | Biochimica et biophysica acta. 1268(3) |
| ISSN: | 0006-3002 |
| Popis: | We investigated the effects of cAMP on the urokinase-type plasminogen activator (uPA) production in human pre-B lymphoma cell line RC-K8 that is consistently secreting uPA in the conditioned medium. Both Bt2cAMP and PGE1 inhibited the uPA accumulation in a dose-dependent manner. Northern blot analysis and nuclear run-on assay revealed that uPA gene transcription was repressed by Bt2cAMP and the repression was negated by inhibition of de novo protein synthesis by cycloheximide. Pretreatment with H89 (N-[2-(p-bromocinnamyl-amino) ethyl]-5-isoquinoline sulfonamide), a specific cAMP-dependent protein kinase (PKA) inhibitor, strongly inhibited both the PKA activation and the supression of uPA mRNA accumulation induced by cAMP. H85 (N-[2-(N-formyl-p-chlorocinnamyl-amino) ethyl]-5-isoquinoline sulfonamide), which closely resembles H89 in its chemical structure but is not a selective inhibitor of PKA, showed little effect on the regulation of uPA gene regulation by Bt2cAMP. These results suggest that cAMP represses uPA gene transcription in human pre-B lymphoma cells through PKA pathway and in which de novo protein synthesis is required. |
| Databáze: | OpenAIRE |
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