Related Experiment Video

Updated: Jul 23, 2025

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

7.7K

The combined action of the intracellular regions regulates FGFR2 kinase activity

Chi-Chuan Lin1, Lukasz Wieteska1, Guillaume Poncet-Montange2

  • 1School of Molecular and Cellular Biology, and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Communications Biology
|July 14, 2023
PubMed

Insights

Fibroblast growth factor receptor 2 (FGFR2) regulation involves juxtamembrane (JM) and C-terminal tail (CT) interactions. These control receptor tyrosine kinase (RTK) activity, preventing cancer by balancing activation and inhibition.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Receptor tyrosine kinases (RTKs) control cellular processes through phosphorylation.
  • Dysregulated RTK activity, including fibroblast growth factor receptor 2 (FGFR2), is linked to cancer.
  • FGFR2 maintains a regulated mono-phosphorylated state for controlled signaling.

Purpose of the Study:

  • To elucidate the molecular mechanisms governing FGFR2 kinase domain (KD) regulation.
  • To investigate the roles of juxtamembrane (JM) and C-terminal tail (CT) regions in FGFR2 activity.
  • To understand how FGFR2 balances rapid response with restricted ligand-independent activation.

Main Methods:

  • Analysis of combinatorial interactions between FGFR2's JM and CT regions.
  • Investigating the structural basis of kinase domain (KD) dimerization and activity.
  • Studying the temporal recruitment of downstream effector proteins.

Main Results:

  • JM stabilizes the asymmetric dimeric KD necessary for phosphorylation.
  • CT binding opposes dimerization and down-regulates kinase activity.
  • Direct JM-CT binding introduces a delay in downstream effector recruitment, adding a regulatory step.

Conclusions:

  • FGFR2 activity is precisely controlled by intricate JM and CT interactions.
  • These interactions ensure regulated receptor tyrosine kinase (RTK) oligomerization and activation.
  • Understanding these mechanisms is crucial for targeting aberrant FGFR2 signaling in diseases like cancer.

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