EXPRESSION AND BIOLOGICAL-ACTIVITY OF MOUSE FIBROBLAST GROWTH FACTOR-IX

Receptor specificity is an essential mechanism governing the activity of fibroblast growth factors (FGF). To begin to understand the develop mental role of FGF-9/glial activating factor, we have cloned and seque nced the murine FGF 9 cDNA and expressed the protein in mammalian cell s and in Escherichia coli. We demonstrate that the FGF-9 protein is hi ghly conserved between mouse and human. Receptor specificity was deter mined by direct binding to soluble and cell surface forms of FGF recep tor (FGFR) splice variants and by the mitogenic activity on cells, whi ch express unique FGF receptor splice variants. Our data demonstrate t hat FGF-B efficiently activates the ''c'' splice forms of FGFR2 and FG FR3, receptors expressed in potential target cells for FGF-9. Signific antly, FGF-9 also binds to and activates the ''b'' splice form of FGFR 3, thus becoming the first FGF ligand besides FGF-1 to activate this h ighly specific member of the FGF receptor family.