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

我们假设神经干细胞的生长、分化和趋化是由FGFR和Eph之间的分子相互作用调控的。我们的研究重点是通过FGFR-EphA4复合物阐明一种新的信号传导机制。我们对调查结果的总结如下。(1) FGFR-EphA4相互作用的生理意义同时表达FGFR和EphA4的分化后的P19细胞，经肾上腺素刺激可促进FGFR-EphA4复合物的形成，进而激活EphA4反式磷酸化的FGFR。此外，免疫细胞化学研究显示，FGFR和EphA4在P19细胞和神经干细胞上共定位，表明FGFR与EphA4在生理上相互作用。(2)FGFR- epha4复合物的形成通过FGFRFRS2增加FRS2-Ras-MAPK信号传导，FGFRFRS2是众所周知的被FGFR激活的下游分子。我们发现FRS2-FGFR-EphA4在小鼠神经干细胞中形成复合物，这种相互作用增加了Ras-MAPK信号传导。我们的研究结果表明，FGFR-EphA4相互作用对神经发生和再生很重要。

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.