Characterization of FGFRL1, a novel fibroblast growth factor (FGF) receptor preferentially expressed in skeletal tissues.
Clones for a novel transmembrane receptor termed FGFRL1 were isolated from a subtracted, cartilage-specific cDNA library prepared from chicken sterna. Homologous sequences were identified in other vertebrates, including man, mouse, rat and fish, but not in invertebrates such as Caenorhabditis elegans and Drosophila. FGFRL1 was expressed preferentially in skeletal tissues as demonstrated by Northern blotting and in situ hybridization. Small amounts of the FGFRL1 mRNA were also detected in other tissues such as skeletal muscle and heart. The novel protein contained three extracellular Ig-like domains that were related to the members of the fibroblast growth factor (FGF) receptor family. However, it lacked the intracellular protein tyrosine kinase domain required for signal transduction by transphosphorylation. When expressed in cultured cells as a fusion protein with green fluorescent protein, FGFRL1 was specifically localized to the plasma membrane where it might interact with FGF ligands. Recombinant FGFRL1 protein was produced in a baculovirus system with intact disulfide bonds. Similar to FGF receptors, the expressed protein interacted specifically with heparin and with FGF2. When overexpressed in MG-63 osteosarcoma cells, the novel receptor had a negative effect on cell proliferation. Taken together our data are consistent with the view that FGFRL1 acts as a decoy receptor for FGF ligands.
Trueb
Beat
B
ITI Research Institute, University of Bern, P. O. Box 54, CH-3010 Bern, Switzerland. beat.trueb@iti.unibe.ch
Zhuang
Lei
L
Taeschler
Sara
S
Wiedemann
Markus
M
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D015152:Blotting, Northern; D019556:COS Cells; D002356:Cartilage / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002645:Chickens; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015723:Gene Library; D049452:Green Fluorescent Proteins; D006801:Humans; D017403:In Situ Hybridization; D007313:Insecta; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051500:Receptor, Fibroblast Growth Factor, Type 5; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution
D018076:DNA, Complementary; D004220:Disulfides; C417531:FGFRL1 protein, human; C496379:Fgfrl1 protein, mouse; D008024:Ligands; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051500:Receptor, Fibroblast Growth Factor, Type 5; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors