Insights into the role of heparan sulphate in fibroblast growth factor signalling
Insights into the role of heparan sulphate in fibroblast growth factor signalling
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DOI：
10.1042/bst0340442
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发表时间：
2006-06-01
影响因子：
3.9
通讯作者：
Harmer, N. J.
中科院分区：
文献类型：
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作者：
Harmer, N. J.
来自成纤维细胞生长因子(FGFs)的信号对于多种细胞和组织的正确发育和动态平衡至关重要。由于生长因子和受体都与HS结合，而HS或肝素是完全信号传递的绝对必要条件，因此，成纤维细胞生长因子/FGFR(成纤维细胞生长因子受体)信号系统是HS(硫酸肝素)结合蛋白的重要范例。成纤维细胞生长因子信号系统的结构特征已经得到了很好的描述，形成成纤维细胞生长因子-纤维生长因子受体-肝素三元复合体所涉及的每个相互作用的细节都已经阐明。最近的工作主要集中在更深入地了解成纤维细胞生长因子-肝素复合体的性质，证明成纤维细胞生长因子优先结合到共受体上的相似位置，并且成对成对的成纤维细胞生长因子对肝素硫化模式比单独的成纤维细胞生长因子显示出更大的特异性。进一步的工作表明，FGF-FGFR-肝素信号复合体只含有一个肝素分子，当较长的肝素片段用于形成FGF-FGFR-肝素复合体时，糖基上会形成多个复合体。这些观察结果构成了一个模型的基础，在该模型中，FGFs和FGFRs可以相互作用的范围以及与HS的相互作用范围可能导致与两个以上FGFR单元形成复合体。因此，从最初的信号转导事件到形成大的受体簇，HS在成纤维细胞生长因子信号转导过程中起着至关重要的作用。
Signalling from the FGFs (fibroblast growth factors) is crucial for the correct development and homoeostasis of a wide range of cells and tissues. The FGF/FGFR (FGF receptor) signalling system forms an important paradigm for HS (heparan sulphate)-binding proteins, as both the growth factor and receptor bind to HS, and HS or heparin is an absolute requirement for full signalling. The FGF signalling system has been extremely well structurally characterized, and details of each interaction involved in forming a ternary complex of FGF-FGFR-heparin have been elucidated. Recent work has focused on a more thorough understanding of the nature of the FGF-heparin complex in particular, demonstrating that FGFs preferentially bind to similar sites on the co-receptor, and that FGF-FGFR pairs show greater specificity for heparin sulphation patterns than individual FGFs. Further work has suggested that FGF-FGFR-heparin signalling complexes contain one molecule of heparin only, and that when longer fragments of heparin are used to form FGF-FGFR-heparin complexes, multiple complexes form upon the saccharide. These observations form the basis of a model where the range of interactions that FGFs and FGFRs can form with one another and with HS may lead to the formation of complexes with more than two FGFR units. Therefore HS will be crucial to FGF signalling from the initial signalling event to the formation of large receptor clusters.