Abstract
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 language | English |
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Pages (from-to) | 621-626 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 263 |
Issue number | 3 |
DOIs | |
State | Published - 5 Oct 1999 |
Externally published | Yes |
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.
Funding
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.
Funders | Funder number |
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Clore Leadership Programme, Clore Duffield Foundation | |
Israel Academy of Sciences and Humanities |
Keywords
- FGF receptor
- FGF4
- Heparin