Model analysis of difference between EGF pathway and FGF pathway

Satoshi Yamada, Takaharu Taketomi, Akihiko Yoshimura

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


The difference in time course of Ras and mitogen activated protein kinase (MAPK) cascade by different growth factors is considered to be the cause of different cellular responses. We have developed the computer simulation of Ras-MAPK signal transduction pathway containing newly identified negative feedback system, Sprouty, and adaptor molecules. Unexpectedly, negative feedback system did not profoundly affect time course of MAPK activation. We propose the key role of fibroblast growth factor receptor substrate 2 (FRS2) in NGF/FGF pathway for sustained MAPK activation. More Grb2-SOS complexes were recruited to the plasma membrane by binding to membrane-bound FRS2 in FGF pathway than in EGF pathway and caused sustained activation of ERK. The EGF pathway with high concentration of EGF receptor also induced sustained MAPK activation, which is consistent with the results in the PC12 cell overexpressing the EGF receptors. The simulated time courses of FRS2 knock-out cells were consistent with those of the reported experimental results.

Original languageEnglish
Pages (from-to)1113-1120
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2004 Feb 20
Externally publishedYes


  • Epidermal growth factor
  • Fibroblast growth factor
  • Fibroblast growth factor receptor substrate 2
  • Nerve growth factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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