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首页> 外文期刊>Molecular and Cellular Biology >Characterization of a novel protein kinase C response element in the glucagon gene.
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Characterization of a novel protein kinase C response element in the glucagon gene.

机译：胰高血糖素基因中新型蛋白激酶C反应元件的表征。

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To maintain glucose levels in blood within narrow limits, the synthesis and secretion of pancreatic islet hormones are controlled by a variety of neural, hormonal, and metabolic messengers that act through multiple signal transduction pathways. Glucagon gene transcription is stimulated by cyclic AMP and depolarization-induced calcium influx. In this study, the effect of protein kinase C on glucagon gene transcription was investigated. After transient transfection of a glucagon-reporter fusion gene into the glucagon-producing islet cell line alphaTC2, activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated glucagon gene transcription. By 5' deletions, 3' deletions, internal deletion, and oligonucleotide cassette insertion, the TPA-responsive element was mapped to the G2 element (from -165 to -200). Like TPA, overexpression of oncogenic Ras (V-12 Ras) stimulated G2-mediated transcription whereas overexpression of a dominant negative Ras mutant (N-17 Ras) blocked the effect of TPA. A mutational analysis of G2 function and nuclear protein binding indicated that protein kinase C and Ras responsiveness is conferred to the glucagon gene by HNF-3beta functionally interacting with a protein that binds to a closely associated site with sequence similarity to binding sites of Ets family proteins. HNF-3beta belongs to the winged-helix family of transcription factors and has been implicated in the control of cell-specific and developmental gene expression. The results of the present study show that the cell lineage-specific transcription factor HNF-3beta is an essential component of a novel protein kinase C response element in the glucagon gene.
机译：为了将血液中的葡萄糖水平维持在狭窄的范围内，胰岛激素的合成和分泌受到多种神经，激素和代谢信使的控制，这些信使通过多种信号转导途径起作用。胰高血糖素基因的转录受环AMP和去极化诱导的钙内流刺激。在这项研究中，研究了蛋白激酶C对胰高血糖素基因转录的影响。在将胰高血糖素报道基因融合基因瞬时转染到产生胰高血糖素的胰岛细胞系alphaTC2之后，通过12-O-十四烷酰佛波醇13-乙酸盐（TPA）激活的蛋白激酶C刺激了胰高血糖素基因转录。通过5'缺失，3'缺失，内部缺失和寡核苷酸盒插入，TPA响应元件被映射到G2元件（从-165到-200）。像TPA一样，致癌Ras（V-12 Ras）的过表达刺激G2介导的转录，而显性负性Ras突变体（N-17 Ras）的过表达阻止TPA的作用。对G2功能和核蛋白结合的突变分析表明，蛋白激酶C和Ras反应性是通过HNF-3beta与结合在紧密相关位点上的蛋白功能性相互作用而赋予胰高血糖素基因的，该位点与Ets家族蛋白的结合位点具有序列相似性。 HNF-3beta属于有翼螺旋转录因子家族，并已参与细胞特异性和发育基因表达的控制。本研究的结果表明，细胞谱系特异性转录因子HNF-3beta是胰高血糖素基因中新型蛋白激酶C反应元件的重要组成部分。

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