...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Comparison of the intracellular signaling responses by three chimeric fibroblast growth factor receptors in PC12 cells
【24h】

Comparison of the intracellular signaling responses by three chimeric fibroblast growth factor receptors in PC12 cells

机译：PC12细胞中三种嵌合成纤维细胞生长因子受体细胞内信号转导反应的比较

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

Stably transfected PC12 cell lines expressing similar amounts of chimeric receptors composed of the ex- tracellular domain of the human platelet-derived growth factor (PDGF)#beta# receptor and the transmembrane and intra- cellular domains of the fibroblast growth factor receptors (FGFRs) 1, 3, and 4 undergo ligand-induced differentiation. The FGFR1 chimera (PFR1) is the most potent of the three, and PFR4 reqnires more frequent (every 24 hr) addition of ligand to maintain the response. Both PFR1 and -3 also show significant ligand-independent autophosphorylation but PFR4 does not. All of the chimeras activated phospholipase C_#gamma#, Shc, FGFR substrate (FRS)2, and the mitogen-activated protein kinases, ERK1 and 2. PFR4 was moderately weaker in stimulating these effects as well, PFR1 and -3 were compara- ble. None of the chimeras induced Sos association or were coprecipitated with Shc. Cotransfection of a dominant- negative Shc derivative, with tyrosine at 239, 240, and 317 replaced with phenylalanine, in the PFR-expressing cells was without effcct on PDGF-induced neurite outgrowth. The same derivative substantially inhibited the response of these cells to NGF. These results indicate that FGFR1, 3, and 4 (i) are capable of signaling in a similar fashion; (ii) primarily use FRS2 and, perhaps, PLC#gamma#, and (iii) do not utilize Shc. The results also suggest that the principal difference between FGFR1, 3, and 4 is in the strength of the tyrosine kinase activity and that qualitative diffcrences in signaling capacity are likely to be less important.
机译：稳定转染的PC12细胞系表达相似数量的嵌合受体，该嵌合受体由人血小板衍生生长因子（PDGF）＃beta＃受体的胞外域和成纤维细胞生长因子受体（FGFRs）的跨膜域和细胞内域组成1、3和4经历配体诱导的分化。 FGFR1嵌合体（PFR1）是这三种中最有效的，并且PFR4需要更频繁地（每24小时）添加配体以维持反应。 PFR1和-3均也显示出显着的非配体依赖性自磷酸化，而PFR4没有。所有嵌合体激活的磷脂酶C_＃gamma＃，Shc，FGFR底物（FRS）2以及丝裂原激活的蛋白激酶ERK1和2。PFR4在刺激这些作用方面也较弱，PFR1和-3相对较弱。 ble。嵌合体均未引起Sos缔合或与Shc共沉淀。在表达PFR的细胞中，显性阴性Shc衍生物（在239、240和317处的酪氨酸被苯丙氨酸替代）的共转染没有影响PDGF诱导的神经突增生。相同的衍生物基本上抑制了这些细胞对NGF的反应。这些结果表明FGFR1、3和4（i）能够以类似的方式进行信号转导。 （ii）主要使用FRS2，也许使用PLC＃gamma＃，并且（iii）不使用Shc。结果还表明，FGFR1、3和4之间的主要区别在于酪氨酸激酶活性的强度，信号传递能力的定性差异可能不太重要。

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