Heparin differentially regulates the interaction of fibroblast growth factor-4 with FGF receptors 1 and 2

David Aviezer, Michal Safran, Avner Yayon

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Fibroblast growth factor-4 (FGF4), like other FGFs, shares a high affinity for the anionic glycosaminoglycans heparin and heparan sulfate (HS), which in turn enhance FGF-receptor (FGFR) binding and activation. Here we demonstrate using a cell free system that, at low concentrations of heparin, FGF4 binds only to FGFR-2, while much higher heparin levels are required for binding to FGFR-1. Chemical crosslinking of radiolabeled FGF4 to the soluble FGF receptors confirms the preferential formation of FGF4-FGFR-2 complexes under restricted heparin availability, with maximal ligand-receptor interactions at almost 20-fold lower heparin concentrations then those required for the affinity labeling of FGFR-1. In accordance, HS-deficient cells expressing FGFR-2 proliferate in response to FGF4 at extremely low exogenous heparin concentrations, while FGFR-1 expressing cells are completely unresponsive under the same conditions. We suggest that FGFR-2 is the preferred receptor for FGF4 under restricted HS conditions and that the bioavailability of structurally distinct HS motifs may differentially control receptor specificity of FGF4 in vivo.

Original languageEnglish
Pages (from-to)621-626
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - 5 Oct 1999
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to Claudio Basilico for the D-32 FGFR-1 and FGFR-2 cells and to Magda David for excellent technical assistance. This study was supported in part by the Israel Academy for Science and Humanities (A.Y.) and the Clore Foundation (D.A.). A.Y. is an incumbent of the Alvin and Gertrude Levine Career Development Chair of Cancer Research.


  • FGF receptor
  • FGF4
  • Heparin


Dive into the research topics of 'Heparin differentially regulates the interaction of fibroblast growth factor-4 with FGF receptors 1 and 2'. Together they form a unique fingerprint.

Cite this