Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin. Mediation of transcriptional activation by Stat5
| Autor: | Mary Vore, Saul J. Karpen, Michelle O'Brien, Tanmoy C. Ganguly, Fredrick J. Suchy, James F. Hyde |
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| Rok vydání: | 1997 |
| Předmět: |
Receptors
Prolactin Organic Anion Transporters Sodium-Dependent Heterologous Biology Transfection digestive system Rats Sprague-Dawley Interferon-gamma Downregulation and upregulation STAT5 Transcription Factor Animals Phosphorylation Binding site Phosphotyrosine Receptor Cell Nucleus Regulation of gene expression Binding Sites Symporters Sodium DNA General Medicine Milk Proteins Molecular biology Animals Suckling Prolactin Rats DNA-Binding Proteins Kinetics Gene Expression Regulation Liver Thymidine kinase Symporter Trans-Activators Female Carrier Proteins hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Journal of Clinical Investigation. 99:2906-2914 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci119485 |
| Popis: | The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form of the PRL receptor (PRLRL) and Stat5. Deletion analysis mapped the PRLinducible region to -1237 to -758 bp of the ntcp promoter. Linking this 0.5-kb region to a heterologous thymidine kinase (tk) promoter, or linking multimerized ntcp GLEs either upstream of the ntcp minimal promoter (-158 to +47 bp) or the heterologous promoter conferred dose-dependent PRL responsiveness. The short form of the PRL receptor failed to transactivate ntcp GLEs. These results indicate that PRL acts via the PRLRL to facilitate Stat5 binding to ntcp-GLEs and to transcriptionally regulate ntcp. |
| Databáze: | OpenAIRE |
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