Heparin-induced self-association of fibroblast growth factor-alpha - Evidence for two oligomerization processes
Heparin-induced self-association of fibroblast growth factor-alpha - Evidence for two oligomerization processes
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DOI：
10.1074/jbc.272.26.16382
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发表时间：
1997-06-27
影响因子：
4.8
通讯作者：
Waksman, G
中科院分区：
文献类型：
--
作者：
Herr, AB;Ornitz, DM;Waksman, G
成纤维细胞生长因子 - 2（FGF - 2）是一种有效的血管生成因子，它需要肝素进行二聚化以及激活FGF受体酪氨酸激酶。肝素对多种成纤维细胞生长因子的结合可能对于FGF受体的二聚化是必需的。在存在肝素衍生糖类的情况下对FGF - 2进行分析超速离心表明，一种有活性的肝素八糖和一种无活性的类肝素二糖都会诱导成纤维细胞生长因子 - 2自缔合。对数据的分析表明，肝素八糖诱导FGF - 2形成单体 - 二聚体 - 四聚体组装，而二糖诱导单体 - 二聚体平衡。有证据表明，肝素八糖诱导的二聚体构象是一种与肝素顺式排列的FGF - 2分子并排二聚体，而二糖诱导的二聚体是一种头对头二聚体，其中FGF - 2分子与配体反式排列。这些结果，结合先前的研究，支持了这样一种模型，即特定的肝素诱导的FGF - 2并排二聚体的形成对于FGF受体的激活是必需的。
Fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, requires heparin for dimerization and activation of the FGF receptor tyrosine kinase. The binding of multiple fibroblast growth factors by heparin may be necessary for dimerization of the FGF receptor, Analytical ultracentrifugation of FGF-2 in the presence of heparin-derived saccharides shows that both an active heparin octasaccharide and an inactive heparin-like disaccharide induce fibroblast growth factor-2 self-association, Analysis of the data indicates that the heparin octasaccharide induces a monomer-dimer-tetramer assembly of FGF-2 while the disaccharide induces a monomer-dimer equilibrium. Evidence is presented indicating that the dimer conformation induced by the heparin octasaccharide is a side by side dimer with the FGF-2 molecules cis to the heparin, while the disaccharide-induced dimer is a head to head dimer in which FGF-2 molecules are trans to the ligand. These results, combined with previous studies, support the model that formation of a specific side by side heparin-induced FGF-2 dimer is required for activation of the FGF receptor.