Expression and biological activity of mouse fibroblast growth factor-9.
Receptor specificity is an essential mechanism governing the activity of fibroblast growth factors (FGF). To begin to understand the developmental role of FGF-9/glial activating factor, we have cloned and sequenced the murine FGF-9 cDNA and expressed the protein in mammalian cells and in Escherichia coli. We demonstrate that the FGF-9 protein is highly conserved between mouse and human. Receptor specificity was determined by direct binding to soluble and cell surface forms of FGF receptor (FGFR) splice variants and by the mitogenic activity on cells, which express unique FGF receptor splice variants. Our data demonstrate that FGF-9 efficiently activates the "c" splice forms of FGFR2 and FGFR3, receptors expressed in potential target cells for FGF-9. Significantly, FGF-9 also binds to and activates the "b" splice form of FGFR3, thus becoming the first FGF ligand besides FGF-1 to activate this highly specific member of the FGF receptor family.
Santos-Ocampo
S
S
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110, USA.
Colvin
J S
JS
Chellaiah
A
A
Ornitz
D M
DM
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D004926:Escherichia coli; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors; D014644:Genetic Variation; D006133:Growth Substances / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; C496459:FGF9 protein, human; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D006133:Growth Substances; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors