Expression and biological activity of mouse fibroblast growth factor-9

Expression and biological activity of mouse fibroblast growth factor-9
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DOI:
10.1074/jbc.271.3.1726
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发表时间:
1996-01-19
影响因子:
4.8
通讯作者:
Ornitz, DM
Ornitz, DM
中科院分区:
生物学2区
文献类型:
--
作者:
SantosOcampo, S;Colvin, JS;Ornitz, DM

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受体特异性是控制成纤维细胞生长因子(FGF)活性的重要机制。为了开始了解FGF-9/胶质细胞活化因子的发育作用,我们克隆并测序了鼠FGF 9 cDNA,并在哺乳动物细胞和大肠杆菌中表达了该蛋白。我们证明FGF-9蛋白在小鼠和人之间是高度保守的。受体特异性通过与可溶性和细胞表面形式的FGF受体(FGFR)剪接变体的直接结合以及对表达独特FGF受体剪接变体的细胞的促有丝分裂活性来确定。我们的数据表明,FGF-B有效地激活FGFR 2和FGFR 3的“c "剪接形式,这些受体在FGF-9的潜在靶细胞中表达。值得注意的是,FGF-9还结合并激活FGFR 3的“b "剪接形式,从而成为除了FGF-1之外第一个激活FGF受体家族的这种高度特异性成员的FGF配体。
Receptor specificity is an essential mechanism governing the activity of fibroblast growth factors (FGF). To begin to understand the developmental role of FGF-9/glial activating factor, we have cloned and sequenced the murine FGF 9 cDNA and expressed the protein in mammalian cells and in Escherichia coli. We demonstrate that the FGF-9 protein is highly conserved between mouse and human. Receptor specificity was determined by direct binding to soluble and cell surface forms of FGF receptor (FGFR) splice variants and by the mitogenic activity on cells, which express unique FGF receptor splice variants. Our data demonstrate that FGF-B efficiently activates the ''c'' splice forms of FGFR2 and FGFR3, receptors expressed in potential target cells for FGF-9. Significantly, FGF-9 also binds to and activates the ''b'' splice form of FGFR3, thus becoming the first FGF ligand besides FGF-1 to activate this highly specific member of the FGF receptor family.