Identification and characterization of a novel member of the fibroblast growth factor family

Abstract

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 novel human gene (1419 bp) encodes for a protein of 216 a.a. with a molecular weight of 22 kDa. The FGF-13 sequence contains an amino-terminal hydrophobic region of 23 a.a. characteristic of a signal secretion sequence. FGF-13 is most homologous, 70% similarity at the amino acid level, to FGF-8. Northern hybridization analysis demonstrated prominent expression of FGF-13 in human foetal and adult brain, particularly in the cerebellum and cortex. In proliferation studies with BaF3 cells, FGF-13 preferentially activates cell clones expressing either FGF receptor variant, 3-IIIc or 4. The signal transduction pathways of FGF-13 and FGF-2 were compared in rat hippocampal astrocytes. The two FGFs induce an equivalent level of tyrosine phosphorylation of mitogen-activated 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 decarboxylase immunopositive neurons, the level of high-affinity gamma-aminobutyric acid (GABA) uptake, and choline acetyltransferase enzyme activity. The GABAergic neuronal response to FGF-13 treatment is rapid with a significant increase occurring within 72 h. We have identified a novel member of the FGF family that is expressed in the central nervous system (CNS) and increases the number as well as the level of phenotypic differentiation of cortical neurons in vitro.

Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and -4, in bovine antral follicles

“…Which ligand(s) might activate FGFR3c and FGFR4 in follicles remains to be clarified. FGF-1, -2, -4, -8, -9 and -13 efficiently activate FGFR3c and -4 (Ornitz et al 1996, Greene et al 1998. In cattle, Fgf1 and Fgf2 expression was predominantly localized to theca cells (Berisha et al 2004), and Fgf2 expression increased with estradiol content (Berisha et al 2004) as did the expression of Fgfr3c in granulosa cells in the present study.…”

Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas

“…The growth factor is likely to be mitogenic for the melanoma cells because it stimulates the mitogen-activated protein kinase pathway (Ref. 77 …”

Roles of intracellular fibroblast growth factors in neural development and functions

“…Frame-shift mutation in the exon 4 of FGF14 gene and DNA polymorphisms is found in patients with inherited ataxias [19].…”

“…Early studies showed that FGF13 could induce tyrosine phosphorylation of mitogen-activated protein kinase (MAPK) and phospholipase C-gamma (PLC-γ) in hippocampal astrocytes [19]. Treatment of neuronal cultures from rat embryonic cortex with FGF13 increased the number of neurons containing gamma-aminobutyric acid (GABA) and choline acetyltransferase enzymes [19].…”