title: Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction.
abstract: Fibroblast growth factor (FGF) receptor (FGFR) gene family consists of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation. Here we have characterized the binding of different FGFs to FGFR-4. Our results establish an FGF binding profile for FGFR-4 with aFGF having the highest affinity, followed by K-FGF/hst-1 and bFGF. In addition, FGF-6 was found to bind to FGFR-4 in ligand competition experiments. Interestingly, the FGFR-4 gene was found to encode only the prototype receptor in a region where both FGFR-1 and FGFR-2 show alternative splicing leading to differences in their ligand binding specificities and to secreted forms of these receptors. Ligands binding to FGFR-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides, which differed from those phosphorylated in FGFR-1-expressing cells. Specifically, the FGFR-1-expressing cells showed a considerably more extensive tyrosine phosphorylation of PLC-gamma than the FGFR-4-expressing cells. Structural and functional specificity within the FGFR family exemplified by FGFR-4 may help to explain how FGFs perform their diverse functions.
authors.affiliation: Department of Pathology, University of Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Vainikka
authors.forename: J
authors.initials: J
authors.lastname: Partanen
authors.forename: P
authors.initials: P
authors.lastname: Bellosta
authors.forename: F
authors.initials: F
authors.lastname: Coulier
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: C
authors.initials: C
authors.lastname: Basilico
authors.forename: M
authors.initials: M
authors.lastname: Jaye
authors.forename: K
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D005091:Exons; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D014443:Tyrosine; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases