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Mol Endocrinol
2005 Aug 01;198:2035-46. doi: 10.1210/me.2004-0531.
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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.
Haas D
,
White SN
,
Lutz LB
,
Rasar M
,
Hammes SR
.
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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.
Barletta,
Characterization of the interactions of estrogen receptor and MNAR in the activation of cSrc.
2004, Pubmed
Barletta,
Characterization of the interactions of estrogen receptor and MNAR in the activation of cSrc.
2004,
Pubmed
Boonyaratanakornkit,
Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases.
2001,
Pubmed
,
Xenbase
Cato,
Rapid actions of steroid receptors in cellular signaling pathways.
2002,
Pubmed
Edwards,
Regulation of signal transduction pathways by estrogen and progesterone.
2005,
Pubmed
Gallo,
Stimulation of Xenopus oocyte maturation by inhibition of the G-protein alpha S subunit, a component of the plasma membrane and yolk platelet membranes.
1995,
Pubmed
,
Xenbase
Gill,
Androgens promote maturation and signaling in mouse oocytes independent of transcription: a release of inhibition model for mammalian oocyte meiosis.
2004,
Pubmed
Hammes,
Steroids and oocyte maturation--a new look at an old story.
2004,
Pubmed
,
Xenbase
Kousteni,
Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity.
2001,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Lutz,
G protein beta gamma subunits inhibit nongenomic progesterone-induced signaling and maturation in Xenopus laevis oocytes. Evidence for a release of inhibition mechanism for cell cycle progression.
2000,
Pubmed
,
Xenbase
Lutz,
Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation.
2001,
Pubmed
,
Xenbase
Lutz,
Selective modulation of genomic and nongenomic androgen responses by androgen receptor ligands.
2003,
Pubmed
,
Xenbase
Maller,
Regulation of oocyte maturation.
1980,
Pubmed
,
Xenbase
Nanevicz,
Thrombin receptor activating mutations. Alteration of an extracellular agonist recognition domain causes constitutive signaling.
1996,
Pubmed
,
Xenbase
Pietras,
Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells.
1977,
Pubmed
Razandi,
Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells.
1999,
Pubmed
Razandi,
Plasma membrane estrogen receptors exist and functions as dimers.
2004,
Pubmed
Razandi,
ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions.
2002,
Pubmed
Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase
Shaul,
Rapid activation of endothelial nitric oxide synthase by estrogen.
1999,
Pubmed
Sheng,
Regulation of Xenopus oocyte meiosis arrest by G protein betagamma subunits.
2001,
Pubmed
,
Xenbase
Simoncini,
Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase.
2000,
Pubmed
Song,
Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation.
2002,
Pubmed
Spivack,
Microinjection of pp60v-src into Xenopus oocytes increases phosphorylation of ribosomal protein S6 and accelerates the rate of progesterone-induced meiotic maturation.
1984,
Pubmed
,
Xenbase
Spivack,
Phosphorylation and protein synthetic events in Xenopus laevis oocytes microinjected with pp60v-src.
1985,
Pubmed
,
Xenbase
Unni,
Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence.
2004,
Pubmed
Vadlamudi,
Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha.
2001,
Pubmed
Vu,
Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation.
1991,
Pubmed
,
Xenbase
Wong,
Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade.
2002,
Pubmed
Wyckoff,
Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i).
2001,
Pubmed
