Receptor Binding and Mitogenic Properties of Mouse Fibroblast Growth Factor 3
MODULATION OF RESPONSE BY HEPARIN (*)
- Marc Mathieu,
- Eric Chatelain(§),
- David Ornitz(¶),
- Janine Bresnick,
- Ivor Mason(**),
- Paul Kiefer and
- Clive Dickson(§§)
- §§ To whom correspondence should be addressed. Tel.: 44-171-269-3336; Fax: 44-171-269-3094.
Abstract
fgf3 has been implicated in the embryonic and fetal development of the mouse and as an oncogene in murine breast cancer. We describe
a procedure to purify the product of the mouse fgf3 gene and show it to be a potent mitogen for some epithelial cell lines. Using a receptor binding competition assay, Fgf3
was shown to bind with high affinity to the IIIb isoforms of Fgf receptor (FgfR) 1 and FgfR2 (ID
= 
0.8 nM) and with a lower affinity to the IIIc variant of FgfR2 (ID
= 
9 nM). No competition for the binding of 
I-Fgf1 was observed for FgfR1 (IIIc), FgfR3 (IIIb and IIIc), or FgfR4. Mitogenicity assays using BaF3 cells containing individual
Fgf receptors showed a pattern of response in agreement with the receptor binding results. A comparison of two mammary epithelial
cell lines showed a marked difference of potency and dependence upon heparin in their response to mouse Fgf3, suggesting a
complex interaction between the ligand and its low and high affinity receptors.
Footnotes
-
↵§ Supported by a European Commission training fellowship (ERBCHBGCT920102) under the Human Capital and Mobility Programme.
-
↵¶ Supported by the Beckman Young Investigator Program and National Institutes of Health Grant CA60673. Present address: Dept. of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110.
-
↵* Part of this work was supported by the Wellcome trust and the Trustees of Guy's Hospital. 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.
-
↵1 The abbreviations used are:
- FgfR
-
Fgf receptor
- DMEM
-
Dulbecco's modified Eagle's medium
- PCR
-
polymerase chain reaction
- kbp
-
kilobase pair(s).
-
↵2D. Ornitz, unpublished observation.
-
↵3M. Mathieu, P. Acland, F. Fuller-Pace, M. Dixon, P. Kiefer, and C. Dickson, unpublished data.
-
↵4J. Bresnick, unpublished data.
-
- Received June 9, 1995.
- Revision received August 3, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
