IDENTIFICATION AND CHARACTERIZATION OF A NOVEL MEMBER OF THE FIBROBLAST GROWTH-FACTOR FAMILY

A new member of the fibroblast growth factor (FGF) family, FGF-13, has been molecularly cloned as a result of high throughput sequencing of a human ovarian cancer cell library. The open reading frame of the nov el human gene (1419 bp) encodes for a protein of 216 a.a. with a molec ular weight of 22 kDa. The FGF-13 sequence contains an amino-terminal hydrophobic region of 23 a.a. characteristic of a signal secretion seq uence. FGF-13 is most homologous, 70% similarity at the amino acid lev el, to FGF-8. Northern hybridization analysis demonstrated prominent e xpression of FGF-13 in human foetal and adult brain, particularly in t he cerebellum and cortex. In proliferation studies with BaF3 cells, FG F-13 preferentially activates cell clones expressing either FGF recept or variant, 3-IIIc or 4. The signal transduction pathways of FGF-13 an d FGF-2 were compared in rat hippocampal astrocytes. The two FGFs indu ce an equivalent level of tyrosine phosphorylation of mitogen-activate d protein kinase (MAPK) and c-raf activation. However, FGF-13 is more effective than FGF-2 in inducing the phosphorylation of phospholipase C-gamma (PLC-gamma). Treatment of neuronal cultures from rat embryonic cortex with FGF-13 increases the number of glutamic acid decarboxylas e immunopositive neurons, the level of high-affinity gamma-aminobutyri c acid (GABA) uptake, and choline acetyltransferase enzyme activity. T he GABAergic neuronal response to FGF-13 treatment is rapid with a sig nificant increase occurring within 72 h. We have identified a novel me mber of the FGF family that is expressed in the central nervous system (CNS) and increases the number as well as the level of phenotypic dif ferentiation of cortical neurons in vitro.