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, Clive Dickson

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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 = ∼0.8 nM) and with a lower affinity to the IIIc variant of FgfR2 (ID50 = ∼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.

Original languageEnglish
Pages (from-to)24197-24203
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number41
DOIs
StatePublished - Oct 13 1995

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