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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Wakayama Medical University
• Principal Investigator: YOKOTE Hideyuki Wakayama Medical University, Molecular medicine, Assistant professor, 付置研究所, 助手 (60316122)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Kazushige Wakayama Medical University, Molecular medicine, professor, 付置研究所, 教授 (60178548) ; JING Xuefeng Wakayama Medical University, Molecular medicine, Assistant professor, 付置研究所, 助手 (70316123)
• Project Period (FY): 2003 – 2004
• Keywords: FGFR / Eph / Neural stem cell

Research Abstract

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 interaction
Ephrin 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 FGFR
FRS2 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.