Study of a novel signal transduction pathway mediated by fibroblast growth factor receptor(FGFR)

成纤维细胞生长因子受体（FGFR）介导的新型信号转导通路的研究

• 批准号: 15590251
• 负责人: YOKOTE Hideyuki
• 金额: $ 2.3万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590251/
• 关键词: FGFR; Eph; Neural stem cell

We hypothesized that neural stem cell growth, differentiation and chemotaxsis are regulated by molecular interaction between FGFR and Eph. Our study is focused on elucidation of a novel signaling mechamism through FGFR-EphA4 complex. Our summary of findings are described bellow.(1)Physiological significance of FGFR-EphA4 interactionEphrin stimulation of differentiated P19 cellls expressing both FGFR and EphA4 promoted FGFR-EphA4 complex formation and then activated EphA4 trans-phosphorylated FGFR. Futhermore, colocalization of FGFR and EphA4 on P19 cells and neural stem cells was shown by immunocytochemical study, indicating that FGFR interacts with EphA4 phisiologically.(2)FGFR-EphA4 complex formation increased FRS2-Ras-MAPK signaling through FGFRFRS2 is well known as a down strem molecule activated by FGFR. We found a complex formation of FRS2-FGFR-EphA4 in mouse neural stem cells and this interaction increasesd Ras-MAPK signaling.Our results suggested that FGFR-EphA4 interaction was important for neurogenesis and regeneration.

我们推测，神经干细胞的生长，分化和趋化性的调节FGFR和Eph之间的分子相互作用。我们的研究重点是阐明一种新的信号转导机制，通过FGFR-EphA 4复合物。我们的研究结果总结如下。（1）FGFR-EphA 4相互作用的生理意义Ephrin刺激表达FGFR和EphA 4的分化的P19细胞促进FGFR-EphA 4复合物的形成，然后激活EphA 4反式磷酸化的FGFR。免疫细胞化学研究显示FGFR和EphA 4在P19细胞和神经干细胞上共定位，表明FGFR与EphA 4在生理上相互作用。（2）FGFR-EphA 4复合物的形成通过FGFRFRS 2增加FRS 2-Ras-MAPK信号传导，众所周知，FGFRFRS 2是由FGFR激活的下行斯特雷姆分子。我们在小鼠神经干细胞中发现FRS 2-FGFR-EphA 4复合物的形成，这种相互作用增强了Ras-MAPK信号，我们的结果表明FGFR-EphA 4相互作用在神经发生和再生中是重要的。