title: 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.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Greene
authors.forename: Y L
authors.initials: YL
authors.lastname: Li
authors.forename: P A
authors.initials: PA
authors.lastname: Yourey
authors.forename: J
authors.initials: J
authors.lastname: Gruber
authors.forename: K C
authors.initials: KC
authors.lastname: Carter
authors.forename: B K
authors.initials: BK
authors.lastname: Shell
authors.forename: P A
authors.initials: PA
authors.lastname: Dillon
authors.forename: C
authors.initials: C
authors.lastname: Florence
authors.forename: D R
authors.initials: DR
authors.lastname: Duan
authors.forename: A
authors.initials: A
authors.lastname: Blunt
authors.forename: D M
authors.initials: DM
authors.lastname: Ornitz
authors.forename: S M
authors.initials: SM
authors.lastname: Ruben
authors.forename: R F
authors.initials: RF
authors.lastname: Alderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D003001:Cloning, Molecular; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000737:chemistry; D010641:Phenotype; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
chemical_list: D011994:Recombinant Proteins; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors