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
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DOI：
10.1074/jbc.m300281200
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发表时间：
2003-09-05
影响因子：
4.8
通讯作者：
Wiedemann, M
中科院分区：
文献类型：
--
作者：
Trueb, B;Zhuang, L;Wiedemann, M
从鸡胸骨制备的消减软骨特异性cDNA文库中分离出一种新的跨膜受体FGFRL 1的克隆。同源序列在其他脊椎动物，包括人，小鼠，大鼠和鱼类中被鉴定，但在无脊椎动物如秀丽隐杆线虫和果蝇中没有。通过北方印迹和原位杂交证实FGFRL 1在骨骼组织中优先表达。在其他组织如骨骼肌和心脏中也检测到少量的FGFRL 1 mRNA。新蛋白含有三个胞外Ig样结构域，与成纤维细胞生长因子（FGF）受体家族成员相关。然而，它缺乏通过转磷酸化进行信号转导所需的细胞内蛋白酪氨酸激酶结构域。当在培养的细胞中作为与绿色荧光蛋白的融合蛋白表达时，FGFRL 1特异性地定位于质膜，在那里它可能与FGF配体相互作用。重组FGFRL 1蛋白在具有完整二硫键的杆状病毒系统中产生。与FGF受体类似，表达的蛋白质与肝素和FGF 2特异性相互作用。当在MG-63骨肉瘤细胞中过表达时，这种新型受体对细胞增殖产生负面影响。总之，我们的数据与FGFRL 1作为FGF配体的诱饵受体的观点一致。
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.