RECEPTOR-BINDING AND HEPARIN-BINDING DOMAINS OF BASIC FIBROBLAST GROWTH-FACTOR
RECEPTOR-BINDING AND HEPARIN-BINDING DOMAINS OF BASIC FIBROBLAST GROWTH-FACTOR
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DOI：
10.1073/pnas.85.7.2324
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发表时间：
1988-04-01
影响因子：
11.1
通讯作者：
GUILLEMIN, R
中科院分区：
文献类型：
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作者：
BAIRD, A;SCHUBERT, D;GUILLEMIN, R
碱性成纤维细胞生长因子的一级结构中有两个功能区，它们与成纤维细胞生长因子受体相互作用，结合放射性标记的肝素，并调节细胞对成纤维细胞生长因子的反应。来源于这两个功能区的多肽可以作为成纤维细胞生长因子活性的部分激动剂和拮抗剂。当3T3成纤维细胞受到成纤维细胞生长因子刺激时，与成纤维细胞生长因子-(24-68)-NH2和成纤维细胞生长因子-(106-115)NH2序列相关的多肽抑制胸腺嘧啶核苷的掺入，但对血小板衍生生长因子或表皮生长因子处理的3T3成纤维细胞无影响。它们还具有部分激动剂活性，在没有外源成纤维细胞生长因子的情况下进行测试时，可以刺激DNA合成。这些活性多肽对A431细胞上表皮生长因子与其受体的结合没有影响，它们可以调节成纤维细胞生长因子对内皮细胞黏附的影响，但不能调节纤维连接蛋白的作用。这些结果表明，设计能够抑制成纤维细胞生长因子生物学效应的特定的成纤维细胞生长因子类似物是可能的。
Two functional domains in the primary stucture of basis fibroblast growth factor (FGF) have been identified on the basis of their ability to interact with the FGF receptor, bind radiolabeled heparin, and modulate the cellular response to FGF. Peptides derived from these two functional domains can act as partial agonists and antagonists in biological assays of FGF activity. Peptides related to the sequences of FGF-(24-68)-NH2 and FGF-(106-115)NH2 inhibit thymidine incorporation into 3T3 fibroblasts when they are stimulated by FGF but have no effect when the cells are treated with either platelet-derived growth factor or epidermal growth factor. They also possess partial agonist activity and can stimulate DNA synthesis when tested in the absence of exogenous FGF. The active peptides have no effect on the binding of epidermal growth factor to its receptor on A431 cells and they can modulate the effects of FGF, but not fibronectin, on endothelial cell adhesion. The results suggest the possibility of designing specific analogs of FGF that are capable of inhibiting the biological effects of FGF.