成纤维细胞生长因子与其受体相互作用及其抑制剂的研究进照

成纤维细胞生长因子(FGF)有许多重要的生理功能,并与肿瘤的形成有关.为了弄清FGF与成纤维细胞生长因子受体(FGFR)相互作用的机制,人们对FGF和RGFR的各个结合结构域进行了深入、细致的研究,定位了aFGF、bFGF的肝素结合区、bFGF的受体结合区、FGF受体的肝素结合区、配体结合区和FGF受体相互结合区,提出了两个FGF与FGFR相互作用的模型,在此基础上设计了FGF的核酸类、糖类和多肽类抑制剂,为寻找新一代抗癌药物打下了理论基础.     

成纤维细胞生长因子的双受体系统

成纤维细胞生长因子(FGFs)对于细胞代谢的刺激作用是通过双受体系统（dual-receptor system）介导的.该系统包括一个酪氨酸激酶受体家族(FGFRs)及肝素硫酸蛋白多糖(HSPG).目前已知有4种FGFRs基因,其转录过程表现出剪切多样性.FGFs与FGFRs的结合表现出交叉特异性.HSPG可促进FGFs与FGFRs的结合和受体二聚体的形成,并增强FGFs对细胞调控的精度.FGFRs通过激活不同下游信号分子影响细胞有丝分裂、神经细胞轴突生长、胚胎发育等.     

成纤维细胞生长因子的临床转化及相关新药研究进展

成纤维细胞生长因子;创伤修复;代谢调控;成纤维细胞生长因子受体抑制剂     

人成纤维细胞生长因子受体2的研究进展

人成纤维细胞生长因子受体（FGFRs)家族在细胞的增殖、分化、血管生成、胚胎及骨骼发育和在与生长发育相关的进程中起着十分重要的作用。成纤维细胞生长因子受体2（FGFR2）是该家族4个成员中的一员,本文就其结构特点及与骨骼发育、肿瘤形成和其他疾病的关系加以综述。     

成纤维细胞生长因子研究进展

成纤维细胞生长因子（ＦＧＦ）家族至少有七个成员,有些成员是原癌基因的产物。它们对多种细胞的生长与分化具有调节作用。该家族存在两类受体,高亲和力受体具有酷氨酸蛋白激酶活性,低亲和力受体为肝素受体。ＦＧＦ对神经生长因子、血小板衍生生长因子的表达有一定调控作用。     

成纤维细胞生长因子的结构与功能研究进展

成纤维细胞生长因子(FGF)是一种重要的多肽生长因子,它可分为酸性(aFGF)和碱性(bFGF)两类.这两类 FGF 在结构与功能的许多方面相似而又有所不同,特别是在肝素结合力以及肝素依赖性上的差异,引起人们的研究兴趣.文中从 FGF 功能区研究,肝素作用机理和结构特征等方面概述了 FGF 结构与功能关系的研究进展.FGF 结构与功能关系的阐明,不仅有助于揭示生物大分子的活性调节机理,也有助于推动 FGF 临床应用研究的开展.     

碱性成纤维细胞生长因子研究进展

碱性成纤维细胞生长因子是细胞生长和分化的重要调节因子,具有促血管生成、细胞增殖、细胞趋化、细胞迁移等活性,在细胞分化和机体发育过程中发挥重要作用。碱性成纤维细胞生长因子通过与细胞膜表面的特异性配体结合,进而引发细胞内的一系列级联反应,从而产生各种生物学效应。本文对碱性成纤维细胞生长因子的生物学基础、信号转导、生物学功能以及临床应用研究进展作一综述。     

碱性成纤维细胞生长因子研究进展

碱性成纤维细胞生长因子是一种在体内分布广泛、生理功能重要的生长因子,本文综合讨论了其家族成员、分子结构、生物学功能、作用机理和研究趋向等问题。     

成纤维细胞生长因子的研究

成纤维细胞生长因子的研究崔亚东（阜阳师范学院生物系,安徽阜阳２３６０３２）关键词成纤维细胞生长因子早在１９４０年,人们发现脑和垂体提取液中含有一种能促进成纤维细胞生长的活性物质。直到１９７４年,该物质才被分离纯化,命名为成纤维细胞生长因子（ＦＧＦ）。...     

Inositolhexakisphosphate (InsP6): An antagonist of fibroblast growth factor receptor binding and activity

Summary Fibroblast growth factors (FGF), which have been implicated in tumor cell growth and angiogenesis, have biological activities that appear to be mediated by both heparinlike extracellular matrix sites and transmembrane tyrosine kinase receptor sites. In the present study, we demonstrated that inositolhexakisphosphate (InsP₆) inhibits basic FGF (bFGF) binding to heparin. Our spectrofluorometric analyses demonstrated that InsP₆ not only bound to bFGF, presumably within the bFGF heparin-binding domain, but also protected bFGF from degradation by trypsin. Also, InsP₆ inhibited the cellular binding of bFGF and other fibroblast growth factor family members such as acidic FGF (aFGF) and K-FGF in a saturable and dose-dependent manner. Furthermore, concentrations as low as 100μM InsP₆ inhibited bFGF-induced DNA synthesis in AKR-2B fibroblasts, as well as the growth of bFGF-and K-FGF-transfected NIH/3T3 cells. Together, these results indicate that InsP₆ may serve as a useful antagonist of FGF activity.     

Towards a resolution of the stoichiometry of the fibroblast growth factor (FGF)-FGF receptor-heparin complex

The 22 members of the fibroblast growth factor (FGF) family have been implicated in cell proliferation, differentiation, survival, and migration. They are required for both development and maintenance of vertebrates, demonstrating an exquisite pattern of affinities for both protein and proteoglycan receptors. Recent crystal structures have suggested two models for the complex between FGFs, FGF receptors (FGFRs) and the proteoglycan heparan sulphate that mediates signalling, and have provided insight into how FGFs show differing affinities for the range of FGFRs. However, the physiological relevance of the two different models has not been made clear. Here, we demonstrate that the two complexes can be prepared from the same protein components, confirming that neither complex is the product of misfolded protein samples. Analyses of the complexes with mass spectrometry and analytical ultracentrifugation show that the species observed are consistent with the crystal structures formed using the two preparation protocols. This analysis supports the contention that both of the crystal structures reflect the state of the molecules in solution. Mass spectrometry of the complexes suggests that the stoichiometry of the complexes is 2 FGF1:2 FGFR2:1 heparin, regardless of the method used to prepare the complexes. These observations suggest that the two proposed complex architectures may both have relevance to the formation of an in vivo signalling complex, with a combination of the two interactions contributing to the formation of a larger focal complex.     

牛脑成纤维细胞生长因子的分离纯化与鉴定

新鲜牛脑组织匀浆液经两步硫酸铵沉淀、CM-Sephadex C50 离子交换层析以及肝素-Sepharose 亲和层析,可得到纯化的酸性和碱性成纤维细胞生长因子(aFGF 和bFGF),分子量分别为13.2kD 和15.2—15.8kD.两种因子均可有效促进3T3细胞的 DNA 合成,ED₅₀分别为15.8ng/ml 和 0.32ng/ml.进一步对 aFGF 的等电点及氨基酸组成做了分析.     

噬菌体展示技术筛选bFGF模拟短肽

目的：通过噬菌体展示技术筛选得到与FGFR结合的bFGF模拟短肽,为bFGF肽类抑制剂的研发提供实验基础。方法：以Balb/c 3T3细胞为靶标,以COS-7细胞作消减,对噬菌体随机七肽库进行4轮生物淘洗,再采用ELISA检测单克隆噬菌体对Balb/c 3T3亲和性和特异性,选取阳性克隆进行DNA测序分析。结果：从富集的噬菌体中获得12个阳性克隆,获得一组疏水性七肽及共同基序PR。结论：利用肽类新药开发的重要工具--噬菌体展示技术,得到2段bFGF的受体结合模拟肽,可望作为bFGF抑制剂的先导肽。