The Modulator of Nongenomic Actions of the Estrogen Receptor (MNAR) Regulates Transcription-Independent Androgen Receptor-Mediated Signaling: Evidence that MNAR Participates in G Protein-Regulated Meiosis in Xenopus laevis Oocytes
| Autor: | Lindsey B. Lutz, Stacy N. White, Melissa Rasar, Derek Haas, Stephen R. Hammes |
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| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic MAP Kinase Signaling System G protein Xenopus Molecular Sequence Data Estrogen receptor Biology Ligands Transfection Models Biological Article Xenopus laevis Endocrinology GTP-Binding Proteins GTP-Binding Protein gamma Subunits Animals Humans Immunoprecipitation Testosterone Amino Acid Sequence Cloning Molecular Molecular Biology Transcription factor Dose-Response Relationship Drug Androgen binding GTP-Binding Protein beta Subunits General Medicine biology.organism_classification Immunohistochemistry Molecular biology Protein Structure Tertiary Cell biology Androgen receptor Meiosis src-Family Kinases Receptors Estrogen Receptors Androgen COS Cells Oocytes Trans-Activators Calcium RNA Interference Signal transduction Co-Repressor Proteins Protein Binding Signal Transduction Transcription Factors Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular Endocrinology. 19:2035-2046 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/me.2004-0531 |
| Popis: | Classical steroid receptors mediate many transcription-independent (nongenomic) steroid responses in vitro, including activation of Src and G proteins. Estrogen-triggered activation of Src can be regulated by the modulator of nongenomic actions of the estrogen receptor (MNAR), which binds to estrogen receptors and Src to create a signaling complex. In contrast, the mechanisms regulating steroid-induced G protein activation are not known, nor are the physiologic responses mediated by MNAR. These studies demonstrate that MNAR regulates the biologically relevant process of meiosis in Xenopus laevis oocytes. MNAR was located throughout oocytes, and reduction of its expression by RNA interference markedly enhanced testosterone-triggered maturation and activation of MAPK. Additionally, Xenopus MNAR augmented androgen receptor (AR)-mediated transcription in CV1 cells through activation of Src. MNAR and AR coimmunoprecipitated as a complex involving the LXXLL-rich segment of MNAR and the ligand binding domain of AR. MNAR and Gbeta also precipitated together, with the same region of MNAR being important for this interaction. Finally, reduction of MNAR expression decreased Gbetagamma-mediated signaling in oocytes. MNAR therefore appears to participate in maintaining meiotic arrest, perhaps by directly enhancing Gbetagamma-mediated inhibition of meiosis. Androgen binding to AR might then release this inhibition, allowing maturation to occur. Thus, MNAR may augment multiple nongenomic signals, depending upon the context and cell type in which it is expressed. |
| Databáze: | OpenAIRE |
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