...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >GRP78/BiP is a novel downstream target of IGF-1 receptor mediated signaling
【24h】

GRP78/BiP is a novel downstream target of IGF-1 receptor mediated signaling

机译：GRP78 /毕普小说下游igf - 1的目标受体介导的信号传导

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

Glucose regulated protein 78/immunoglobulin binding protein (GRP78/BiP) is an endoplasmic reticulum (ER) chaperone protein and master regulator of the unfolded protein response (UPR). The response of GRP78 to overt pharmacologically induced ER stress is well established, whereas the modulation of GRP78 to physiologic changes is less characterized. In this study, we examined the regulation of GRP78 in response to reduced IGF-1 growth factor signaling, a common consequence of calorie restriction (CR). ER chaperone protein expression was quantified in cell lysates prepared from the livers of calorie restricted (CR) and ad libitum fed mice, as well as MEFs grown in normal medium or serum starved. The requirement of IGF-1 signaling on GRP78 expression was studied using MEFs with IGF-1 receptor overexpression (R+) or deletion (R-), and the regulatory mechanism was examined using mTORC1 and PI3K inhibitors, as well as R- cells with knockdown of transcription factor FOXO1 compared to shRNA control. We observed a 40% reduction in GRP78 protein expression in CR mice and in serum-starved MEF cells. R- cells had drastically reduced AKT phosphorylation and exhibited lower levels of ER chaperones, in particular 80% less GRP78. Despite an 80% reduction in GRP78 expression, R- cells were not under chronic ER stress, but were fully capable of activating the UPR. Neither forced expression of FOXO1-AAA nor knockdown of FOXO1 in R- cells affected GRP78 expression. In conclusion, we report that IGF-1 receptor signaling regulates GRP78 expression via the PI3K/AKT/mTORC1 axis independent of the canonical UPR and FOXO1.
机译：葡萄糖调节蛋白78 /免疫球蛋白结合蛋白(GRP78 /毕普)是一种内质的网(ER)伴护蛋白质和主人监管机构展开的蛋白质反应(UPR)。GRP78的反应明显的药物诱导ER应激是良好的,而GRP78生理变化的调制少的特点。GRP78的规定以响应降低igf - 1生长因子信号,一个共同的热量限制的结果(CR)。伴护蛋白表达是量化肝脏的细胞溶解产物准备卡路里限制(CR)和随意喂老鼠,mef生长在正常中或血清饥饿。igf - 1的要求对GRP78信号表达式,研究了使用mef和igf - 1受体过度(R +)或删除(R -),检查使用和监管机制mTORC1和PI3K抑制剂,以及R -细胞转录因子FOXO1击倒相比,成分控制。减少GRP78蛋白表达在CR老鼠而在serum-starved MEF细胞。大大减少了一种蛋白激酶磷酸化和表现出低水平的陪伴,特定的GRP78少80%。减少GRP78的表达,R -细胞没有在慢性ER应激下,但被完全有能力激活UPR。FOXO1 FOXO1-AAA还是击倒的R -细胞GRP78的表达的影响。报告说,igf - 1受体信号调节通过PI3K / AKT GRP78表达/ mTORC1轴独立的规范UPR FOXO1。

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