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Updated: Oct 7, 2026

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
07:32

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

Published on: September 30, 2019

Selective inhibition of fibroblast growth factor (FGF)-stimulated mitogenesis by a FGF receptor-1-derived

D J Dunican1, E J Williams, F V Howell

  • 1Molecular Neurobiology Group, MRC Centre for Developmental Neurobiology, Kings College London, London Bridge, London SE1 1UL, United Kingdom.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|May 25, 2001
PubMed

Insights

A novel phosphopeptide targeting fibroblast growth factor receptor (FGFR)-1 inhibits FGF-mediated cell growth. This peptide, FGFR730(p)Y, may block Shc protein binding, impacting mitogenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Fibroblast growth factor receptor (FGFR)-1 activation involves tyrosine phosphorylation outside its catalytic site.
  • The physiological role of phosphorylation at Tyr730 on FGFR-1 remains debated, despite potential binding sites for phosphotyrosine-interacting molecules.

Purpose of the Study:

  • To investigate the functional significance of the Tyr730 residue in FGFR-1 signaling.
  • To determine if a phosphopeptide mimic of Tyr730 can inhibit FGF-mediated cellular responses.

Main Methods:

  • Synthesis of a cell-permeant phosphopeptide mimic of the FGFR-1 Tyr730 site (FGFR730(p)Y).
  • Assessing the effect of FGFR730(p)Y on FGF-mediated mitogenesis and responses to other growth factors.
  • Investigating the interaction of FGFR730(p)Y with intracellular signaling proteins, including Shc and components of the Erk-kinase cascade.

Main Results:

  • FGFR730(p)Y specifically inhibited FGF-mediated mitogenesis without affecting other growth factor responses.
  • The peptide did not inhibit phosphorylation of p90/FRS2 or Erk, indicating it does not block the Erk-kinase cascade.
  • FGFR730(p)Y demonstrated binding to Shc, dependent on both phosphorylated tyrosine and a PTB domain binding determinant.

Conclusions:

  • The Tyr730 site on FGFR-1 plays a role in FGF-mediated mitogenesis.
  • FGFR730(p)Y peptide inhibits mitogenesis likely by competing with the native FGFR-1 Tyr730 site for Shc binding.
  • These findings provide insights into FGFR-1 signaling pathways and potential therapeutic targets.

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