Model analysis of difference between EGF pathway and FGF pathway

Satoshi Yamada, Takaharu Taketomi, Akihiko Yoshimura

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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
Volume314
Issue number4
DOIs
Publication statusPublished - 2004 Feb 20
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinases
Epidermal Growth Factor
Chemical activation
Substrates
Receptor, Fibroblast Growth Factor, Type 2
Feedback
Fibroblast Growth Factor Receptors
Signal transduction
PC12 Cells
Nerve Growth Factor
Fibroblast Growth Factor 2
Cell membranes
Epidermal Growth Factor Receptor
Computer Simulation
Signal Transduction
Intercellular Signaling Peptides and Proteins
Cell Membrane
Membranes
Molecules
Computer simulation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Model analysis of difference between EGF pathway and FGF pathway. / Yamada, Satoshi; Taketomi, Takaharu; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 314, No. 4, 20.02.2004, p. 1113-1120.

Research output: Contribution to journalArticle

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