...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >The ZnR/GPR39 interacts with the CaSR to enhance signaling in prostate and salivary epithelia
【24h】

The ZnR/GPR39 interacts with the CaSR to enhance signaling in prostate and salivary epithelia

机译：ZnR / GPR39与CaSR交互提高信号在前列腺癌和唾液上皮细胞

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

Zinc signaling is mediated by the zinc sensing receptor, ZnR, recently suggested to be the same receptor as G-protein coupled receptor 39, GPR39. However, it is unknown if GPR39 is mediating Zn2+-dependent signaling in prostate and salivary tissue where changes in zinc concentrations are frequent and of physiological significance. Here, we show that GPR39 is mediating Zn2+-dependent Ca2+ responses and is regulating activity of MAP and PI3 pathways in prostate cancer cells, PC3, and ductal salivary gland cells, HSY. We next ask whether ZnR/GPR39 interacts with other GPCR family members. We find that endogenous ZnR/GPR39 activity is regulated by the expression and activity of another cation sensing GPCR, the Ca2+-sensing receptor (CaSR). Although CaSR is not activated by Zn2+, co-expression of CaSR and ZnR/GPR39 synergistically enhances Ca2+ responses in PC3 and HSY cells. Silencing of the CaSR using siRNA or a dominant negative construct reduces the Zn2+-dependent signaling. Importantly, overexpression of GPR39 in HEK293 cells is sufficient to trigger Zn2+-dependent responses. Nevertheless, application of the CaSR agonist spermine, at concentration below its threshold, enhanced Zn2+-dependent Ca2+ response. Our results suggest that the CaSR interacts with ZnR/GPR39 and thereby regulates its activity. Finally, we show that in PC3 cells ZnR/GPR39 is required for mediating the Zn2+-dependent activation of MAPK and PI3K, pathways leading to enhanced cell growth. Importantly, Zn2+-dependent activation of ZnR/GPR39 also enhances the expression of the Ca2+-binding protein S100A4 that is linked to invasion of prostate cancer cells. J. Cell. Physiol. 229: 868-877, 2014.
机译：信号是由锌锌传感受体,ZnR最近建议是相同的受体,受体g蛋白耦合39岁GPR39。然而,它是未知的,如果GPR39调停Zn2 +端依赖信号在前列腺癌和唾液组织中锌浓度的变化频繁和生理意义。我们表明,GPR39调停Zn2 +端依赖Ca2 +的反应和调节活动地图在前列腺癌细胞和PI3通路,生物,公司和导管唾液腺细胞。与其他GPCR是否ZnR / GPR39交互家庭成员。活动是表达和调控另一个阳离子传感GPCR的活动Ca2 +敏感技术受体(CaSR)。不激活Zn2 + co-expression CaSR和ZnR / GPR39协同增强Ca2 +的反应公司在生物和细胞。核或显性负构造减少Zn2 +端依赖信号。过度的GPR39在HEK293细胞中足以引发Zn2 +端依赖反应。然而,CaSR受体激动剂的应用精胺浓度低于阈值,增强Zn2 +端依赖钙离子的反应。结果表明,CaSR交互ZnR / GPR39,从而调节其活性。最后,我们表明,在生物细胞ZnR / GPR39要求中介Zn2 +端依赖激活MAPK和PI3K途径增强细胞生长。激活ZnR / GPR39也增强了Ca2 +绑定S100A4蛋白的表达这是与前列腺癌的侵犯细胞。

著录项

相似文献

  • 外文文献
  • 中文文献
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