title: Receptor binding and mitogenic properties of mouse fibroblast growth factor 3. Modulation of response by heparin.
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 (ID50 = approximately 0.8 nM) and with a lower affinity to the IIIc variant of FgfR2 (ID50 = approximately 9 nM). No competition for the binding of 125I-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.
authors.affiliation: Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Mathieu
authors.forename: E
authors.initials: E
authors.lastname: Chatelain
authors.forename: D
authors.initials: D
authors.lastname: Ornitz
authors.forename: J
authors.initials: J
authors.lastname: Bresnick
authors.forename: I
authors.initials: I
authors.lastname: Mason
authors.forename: P
authors.initials: P
authors.lastname: Kiefer
authors.forename: C
authors.initials: C
authors.lastname: Dickson
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005314:Embryonic and Fetal Development; D004848:Epithelium; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D006493:Heparin; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3