FGF receptor mutations: dimerization syndromes, cell growth suppression, and animal models

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Updated: Oct 2, 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

K Kannan1, D Givol

  • 1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

IUBMB Life
|June 27, 2000
PubMed

Insights

Fibroblast growth factor receptor (FGFR) mutations cause skeletal malformations through gain-of-function mechanisms. Disease severity depends on receptor activation extent and tissue expression, impacting chondrocyte growth.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Fibroblast growth factor receptors (FGFRs) are crucial for development.
  • FGFR mutations are the most common germline mutations in humans, causing over seven skeletal syndromes.
  • Over 75 mutations have been identified, often leading to gain-of-function phenotypes.

Purpose of the Study:

  • To review recent advancements in understanding FGFRs.
  • To emphasize the role of FGFR mutants in skeletal malformations.
  • To explore therapeutic targets for FGFR-related disorders.

Main Methods:

  • Review of existing literature on FGFR mutations and skeletal syndromes.
  • Analysis of the structural basis of receptor dimerization and activation.
  • Utilizing gene-targeted FGFR3 mutant mice and cell line studies.

Main Results:

  • Gain-of-function mutations in FGFRs activate receptors via dimerization, kinase activation, and increased FGF affinity.
  • Disease severity correlates with receptor activation and tissue-specific expression.
  • Paradoxically, FGFR activation inhibits chondrocyte growth through cell-type specific pathways.

Conclusions:

  • Understanding FGFR structure and mutation mechanisms is key to explaining skeletal malformations.
  • FGFR3 signaling pathways are being delineated using mouse models and cell studies.
  • Novel therapeutic targets for FGFR-related skeletal disorders are emerging.

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