Fibroblast Growth Factor (FGF) 3 from Xenopus laevis (XFGF3) Binds with High Affinity to FGF Receptor 2 (*)
- From the Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom and
- Division of Anatomy and Cell Biology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, Guy's Campus, London SE1 9RT, United Kingdom
- § To whom correspondence should be addressed: Viral Carcinogenesis Laboratory, P.O. Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel: 44-71-269-3336; Fax: 44-71-269-3094.
Abstract
We demonstrate that purified fibroblast growth factor (FGF) 3 from Xenopus laevis (XFGF3) activates the mitogen-activated protein kinase pathway and induces DNA synthesis in quiescent cells. To characterize
the high affinity cell surface receptors that mediate these responses, the ligand binding domains of different FGF receptors
(FGFR) were expressed on COS-1 cells, and their affinity for XFGF3 was determined. Unlabeled XFGF3 efficiently competed with
I-FGF1 for binding to the IIIb and IIIc isoforms of FGFR2, giving 50% displacement (ID
) at 0.3-0.8 nM. Higher XFGF3 concentrations were needed to displace 
I-FGF1 from FGFR3 and FGFR1 (ID
4 and 21 nM, respectively), indicating that XFGF3 has a lower affinity for these receptors. No association of XFGF3 with
FGFR4 was found using this assay. FGFR2 isoforms isolated from both mouse and Xenopus showed similar high affinity binding of XFGF3 as determined by direct binding assays (K
values in the range of 0.2-0.6 nM). These results indicate that the binding specificity of XFGF3 is different from that of
other FGFs, and identifies FGFR2 as its high affinity receptor.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- FGF
-
fibroblast growth factor
- FGFR
-
fibroblast growth factor receptor
- XFGF
-
fibroblast growth factor from Xenopus laevis
- MAP
-
mitogen-activated protein
- DMEM
-
Dulbecco's modified Eagle's medium
- RT
-
reverse transcription
- PCR
-
polymerase chain reaction
- PMSF
-
polymethylsulfonyl fluoride
- PBS
-
phosphate-buffered saline
- PAGE
-
polyacrylamide gel electrophoresis.
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↵2M. Mathieu, P. Kiefer, I. Marics, and C. Dickson, unpublished observations.
-
- Received October 20, 1994.
- Revision received December 20, 1994.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
