Receptor binding and mitogenic properties of mouse fibroblast growth factor 3. Modulation of response by heparin.
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.
Mathieu
M
M
Imperial Cancer Research Fund, London, United Kingdom.
Chatelain
E
E
Ornitz
D
D
Bresnick
J
J
Mason
I
I
Kiefer
P
P
Dickson
C
C
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*
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