...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling.
【24h】

Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling.

机译：Akt，ERK和CREB上游调节剂在NCAM和FGF2介导的信号传导中的相对作用。

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

Although a large number of signalling cascades are known to be activated downstream of NCAM, only little is known regarding the hierarchical relationship between the involved molecules in the individual cascades and the level of cross talk between the cascades. Here, we evaluated the requirement of putative upstream signalling cascades for the phosphorylation of the kinases extracellular signal-regulated kinase (ERK) and Akt and the transcription factor cyclic adenosine monophosphate (cAMP) response-element binding protein (CREB) following stimulation of NCAM in rat cerebellar granule neurons with an NCAM ligand, the C3d peptide. NCAM-mediated ERK phosphorylation depended on activation of the fibroblast growth factor receptor (FGFR), Src-family kinases, MEK (MAP and ERK kinase) and G(0)/G(i)-proteins, whereas NCAM-mediated CREB phosphorylation depended on the activity of Src-family kinases and MEK. NCAM-specific Akt phosphorylation depended on cyclic guanosine monophosphate (cGMP) and phosphatidylinositide 3-kinase (PI3K). All three phosphorylation events were independent of activation of the signalling molecules phospholipase C, protein kinase C, protein kinase A, and CamKII, which all have been demonstrated previously to be involved in NCAM signalling. For comparison, we also evaluated the role of upstream signalling cascades on fibroblast growth factor 2 (FGF2)-mediated phosphorylation of ERK, Akt, and CREB and found that FGF2 required the activity of both FGFR and Src-family kinases for phosphorylation of ERK, Akt, and CREB. MEK was required for phosphorylation of ERK and CREB, but not Akt, whereas G(0)/G(i)-proteins were necessary for phosphorylation of Akt and CREB, and cGMP was necessary for Akt phosphorylation. We thus demonstrate that even though NCAM and FGF2 have many signalling features in common, and even though both are known to activate FGFR, there are a number of differences in the intracellular signalling network activated by the NCAM ligand C3d and the FGFR ligand FGF2.
机译：尽管已知有许多信号级联在NCAM的下游被激活，但是对于各个级联中所涉及分子之间的层次关系以及级联之间的串扰水平知之甚少。在这里，我们评估了假定的上游信号级联对细胞外信号调节激酶（ERK）和Akt和转录因子环状单磷酸腺苷（cAMP）反应元件结合蛋白（CREB）磷酸化的激酶的磷酸化的要求。具有NCAM配体C3d肽的大鼠小脑颗粒神经元。 NCAM介导的ERK磷酸化取决于成纤维细胞生长因子受体（FGFR），Src家族激酶，MEK（MAP和ERK激酶）和G（0）/ G（i）蛋白的激活，而NCAM介导的CREB磷酸化取决于Src家族激酶和MEK的活性NCAM特异的Akt磷酸化取决于环状鸟苷单磷酸（cGMP）和磷脂酰肌醇3激酶（PI3K）。所有这三个磷酸化事件均与信号分子磷脂酶C，蛋白激酶C，蛋白激酶A和CamKII的激活无关，而这些分子先前均已被证明参与NCAM信号转导。为了进行比较，我们还评估了上游信号传导级联对成纤维细胞生长因子2（FGF2）介导的ERK，Akt和CREB磷酸化的作用，发现FGF2既需要FGFR又需要Src家族激酶才能使ERK磷酸化， Akt和CREB。 ERK和CREB的磷酸化需要MEK，而Akt则不需要，而Gkt（G）/ G（i）-蛋白对于Akt和CREB的磷酸化是必需的，而cGMP对于Akt磷酸化是必需的。因此，我们证明即使NCAM和FGF2具有许多共同的信号特征，并且即使已知两者都可以激活FGFR，但在NCAM配体C3d和FGFR配体FGF2激活的细胞内信号网络中仍存在许多差异。

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