...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Neuregulin-1-stimulated phosphorylation of GABP in skeletal muscle cells
【24h】

Neuregulin-1-stimulated phosphorylation of GABP in skeletal muscle cells

机译：神经调节蛋白1刺激骨骼肌细胞中GABP的磷酸化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Localization of acetyicholine receptors (AChRs) to neuromuscular synapses is mediated, in part, through selective transcription of AChR genes in myofiber synaptic nuclei. Neuregulin- 1 (NRG-l) is a good candidate for the extracellular signal that induces synapse-specific gene expression, since NRG- 1 is concentrated at synaptic sites and activates AChR synthesis in cultured muscle cells. NRG-1-induced transcription requires activation of Erk and Jnk MAP kinases, but the downstream substrates that mediate this transcriptional response are not known. Previous studies have demonstrated that a consensus binding site for Ets proteins is required both for NRG-1 -induced transcription and for synapse-specific transcription in transgenic mice. This regulatory element binds GABPct, an Ets protein, and GABP/3, a protein that dimerizes with GABPO, raising the possibility that phosphorylation of GABP by MAP kinases induces transcription of AChR genes. To determine whether MAP kinases might directly regulate the activity of GABP, we studied MAP kinase-catalyzed and NRG- 1-induced phosphorylation of GABPci. and GABP/3. We show that GABPct and GABP/3 are phosphorylated in vitro by Erk and by Jnk. Using recombinant proteins containing mutated serine and threonine resides, we show that GABPO~ is phosphorylated predominantly at threonine 280, while serine 170 and threonine 180 are the major phosphorylation sites in GABP/3. We generated antibodies specific to the major phosphorylation site in GABPci. and show that NRG-l stimulates phosphorylation of GABPct at threonine 280 in vivo. These results suggest that GABPct is a target of MAP kinases in NRG- 1-stimulated muscle cells and are consistent with the idea that phosphorylation of GABPi contributes to transcriptional activation of AChR genes by NRG- 1.
机译：乙酰胆碱受体（AChR）在神经肌肉突触中的定位部分是通过肌纤维突触核中AChR基因的选择性转录介导的。神经调节蛋白-1（NRG-1）是诱导突触特异性基因表达的细胞外信号的良好候选者，因为NRG-1集中在突触位点并激活培养的肌肉细胞中的AChR合成。 NRG-1诱导的转录需要激活Erk和Jnk MAP激酶，但介导此转录反应的下游底物尚不清楚。先前的研究表明，转基因小鼠中NRG-1诱导的转录和突触特异性转录均需要Ets蛋白的共有结合位点。该调节元件与Ets蛋白GABPct和与GABPO二聚的蛋白GABP / 3结合，从而增加了MAP激酶使GABP磷酸化诱导AChR基因转录的可能性。为了确定MAP激酶是否可能直接调节GABP的活性，我们研究了MAP激酶催化和NRG-1诱导的GABPci磷酸化。和GABP / 3。我们显示，GABPct和GABP / 3在体外被Erk和Jnk磷酸化。使用含有突变的丝氨酸和苏氨酸的重组蛋白存在，我们表明GABPO〜主要在苏氨酸280磷酸化，而丝氨酸170和苏氨酸180是GABP / 3中的主要磷酸化位点。我们生成了对GABPci中主要磷酸化位点具有特异性的抗体。并且表明NRG-1在体内在苏氨酸280上刺激GABPct的磷酸化。这些结果表明，GABPct是NRG-1刺激的肌肉细胞中MAP激酶的靶标，并且与GABPi的磷酸化有助于NRG-1转录AChR基因的想法相一致。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号