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Serum Response Factor-GATA Ternary Complex Required for Nuclear Signaling by a G-Protein-Coupled Receptor

机译:G蛋白偶联受体的核信号转导所需的血清反应因子-GATA三元复合物

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Endothelins are a family of biologically active peptides that are critical for development and function of neural crest-derived and cardiovascular cells. These effects are mediated by two G-protein-coupled receptors and involve transcriptional regulation of growth-responsive and/or tissue-specific genes. We have used the cardiac ANF promoter, which represents the best-studied tissue-specific endothelin target, to elucidate the nuclear pathways responsible for the transcriptional effects of endothelins. We found that cardiac-specific response to endothelin 1 (ET-1) requires the combined action of the serum response factor (SRF) and the tissue-restricted GATA proteins which bind over their adjacent sites, within a 30-bp ET-1 response element. We show that SRF and GATA proteins form a novel ternary complex reminiscent of the well-characterized SRF-ternary complex factor interaction required for transcriptional induction of c-fos in response to growth factors. In transient cotransfections, GATA factors and SRF synergistically activate atrial natriuretic factor and other ET-1-inducible promoters that contain both GATA and SRF binding sites. Thus, GATA factors may represent a new class of tissue-specific SRF accessory factors that account for muscle- and other cell-specific SRF actions.
机译:内皮素是一类生物活性肽,对神经that衍生和心血管细胞的发育和功能至关重要。这些作用是由两个G蛋白偶联受体介导的,涉及生长反应性和/或组织特异性基因的转录调控。我们已经使用了心脏ANF启动子(代表研究最好的组织特异性内皮素靶标)阐明负责内皮素转录作用的核途径。我们发现,对内皮素1(ET-1)的心脏特异性应答需要血清应答因子(SRF)和组织受限的GATA蛋白(在其30 bp ET-1应答中结合在其相邻位点上)的联合作用元件。我们表明,SRF和GATA蛋白形成了一种新颖的三元复合物,使人想起了对c- fos 的转录诱导响应于生长因子的特征明确的SRF-三元复合物相互作用。在瞬时共转染中,GATA因子和SRF协同激活心房利钠因子和其他同时包含GATA和SRF结合位点的ET-1诱导型启动子。因此,GATA因子可能代表一类新的组织特异性SRF辅助因子,可解释肌肉和其他细胞特异性SRF的作用。

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