Characterization of a Novel Protein (FGFRL1) from Human Cartilage Related to FGF Receptors

Wiedemann, Markus; Trüeb, Beat

doi:10.1006/geno.2000.6332

Cited by 134 publications

(128 citation statements)

References 14 publications

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“…We have tried to reproduce these findings with commercial as well as homemade Northern blots. In relation to the high expression of FGFRL1 in cartilage, we observed only weak expression in pancreas, kidney, and lung (14). 2 It is possible that differences in the sensitivity of the hybridization protocol applied may explain part of the apparent discrepancies.…”

Section: Discussionmentioning

confidence: 74%

“…It should also be noted that the strong signal detected by Kim et al (20) in samples from human pancreas corresponded to a mRNA species of ϳ5 kb that was not found in any other tissue. This species must represent an unusual gene product that clearly differs from the human FGFRL1 mRNA of ϳ3 kb characterized in our study (14). Furthermore, no pancreas-specific expression is supported by data from serial analysis of gene expression (SAGE) published on the internet (www.ncbi.nlm.nih.gov/ SAGE).…”

Section: Discussionmentioning

confidence: 75%

“…Utilizing the information of the chicken sequence and various expressed sequence tags, we were able to clone the homologous proteins from man (GenBank TM accession number AJ277437), mouse (GenBank TM accession number AJ293947), and rat (GenBank TM accession number AJ536020). The sequences for the human and the mouse protein have already been published as short sequence papers (14,15). A strong conservation of the amino acids was observed when the four protein sequences were compared (Fig.…”

Section: Resultsmentioning

confidence: 93%

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Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

Trüeb

Zhuang

Taeschler

et al. 2003

Journal of Biological Chemistry

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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.Most bones of the vertebrate skeleton are formed by a complex process termed endochondral ossification which involves a cartilage intermediate (1). This intermediate represents a highly specialized connective tissue. It consists of a single cell type, the chondrocytes, which are embedded in a rich extracellular matrix (2). Typically, this matrix makes up more than 90% of the cartilage volume and consists of collagens (types II, IX, X, and XI), proteoglycans (aggrecan, small leucine-rich proteins), and glycoproteins (matrilins, COMP).During the first step of endochondral ossification, mesenchymal cells condense and differentiate into chondrocytes (3). These chondrocytes proliferate rapidly and lay down the cartilaginous model of the future bones. The chondrocytes undergo a complex series of distinct developmental stages, including proliferation, maturation, and hypertrophy. The hypertrophic cartilage is calcified and becomes vascularized. Finally, the calcified cartilage is invaded by osteoclasts and osteoblasts, which replace the cartilaginous tissue by bone.Cartilage has become a popular tissue to study cell proliferation and differentiation in vitro (3). When cultivated on plastic dishes, chondrocytes rapidly dedifferentiate into fibroblast-like cells. In three-dimensional lattices, however, the chondrocytes undergo the ordered sequence of events observed during differentiation and maturation of cartilage in vivo. Three stages of chondrocyte differentiation have been defined in vitro: proliferative chondrocytes producing mainly collagen II, hypertrophic chondrocytes producing collagen X, and osteoblast-like cells producing...

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 93%

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Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

Trüeb

Zhuang

Taeschler

et al. 2003

Journal of Biological Chemistry

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“…A fifth nontyrosine kinase FGFR, FGFR5 or FGFRL1, is homologous to FGFR1-4 in the extracellular ligand-binding domain but lacks an intracellular tyrosine kinase domain. Fgfrl1 was originally identified in human cartilage (Wiedemann and Trueb 2000).…”

Section: Fgf Signalingmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

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Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

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“…Loss of function of ndk would allow these factors to travel to more posterior regions, and thus activate FGF receptors outside the head region to trigger ectopic brain formation (figure 6). (Wiedemann & Trueb 2000). Recently, some of our collaborators, Dr Taira's group, identified FGFRL1 from Xenopus (XFGFRL1) and analysed its expression pattern during embryogenesis (Hayashi et al 2004).…”

Section: Alternative 'Capture' Model To Explain Ndk Actionmentioning

confidence: 99%

Brain regeneration from pluripotent stem cells in planarian

Agata

Umesono

2008

Phil. Trans. R. Soc. B

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How can planarians regenerate their brain? Recently we have identified many genes critical for this process. Brain regeneration can be divided into five steps: (1) anterior blastema formation, (2) brain rudiment formation, (3) pattern formation, (4) neural network formation, and (5) functional recovery. Here we will describe the structure and process of regeneration of the planarian brain in the first part, and then introduce genes involved in brain regeneration in the second part. Especially, we will speculate about molecular events during the early steps of brain regeneration in this review. The finding providing the greatest insight thus far is the discovery of the nou-darake (ndk; 'brains everywhere' in Japanese) gene, since brain neurons are formed throughout the entire body as a result of loss of function of the ndk gene. This finding provides a clue for elucidating the molecular and cellular mechanisms underlying brain regeneration. Here we describe the molecular action of the nou-darake gene and propose a new model to explain brain regeneration and restriction in the head region of the planarians.

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Characterization of a Novel Protein (FGFRL1) from Human Cartilage Related to FGF Receptors

Cited by 134 publications

References 14 publications

Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

Fibroblast growth factor signaling in skeletal development and disease

Brain regeneration from pluripotent stem cells in planarian

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