Gallagher J T
Med. Oncology Department, University of Manchester, Christie Hospital, United Kingdom.
Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):239-47.
The complex polymeric structure of heparan sulphate contains intra-chain sequences of sulphated sugar residues that define active sites for the binding and activation of growth factors. The molecular mechanisms of recognition and activation are slowly being revealed at least in the case of the interaction of heparan sulphate with basic fibroblast growth factor. Current data indicate that relatively long but specific binding sequences in heparan sulphate may induce a conformational change in basic fibroblast growth factor exposing a site on the protein that is recognised by signal transducing receptors. Heparan sulphate may also subserve functions of dimerisation of basic fibroblast growth factor and facilitation of receptor transfer by a secondary interaction with the receptor itself. Various models for heparan sulphate mediated induction of mitogenesis by basic fibroblast growth factor have been proposed and there are suggestions that the core protein of plasma membrane heparan sulphate-proteoglycans may participate in the cell signalling process. The vital importance of heparan sulphate in controlling growth factor activities has opened up a new chapter in proteoglycan research and has brought proteoglycans into the mainstream of cell biology. Further investigation of their mode of action is likely to reveal new information on the control of cell growth and development in both embryonic and adult tissues and may suggest novel methods of controlling diseases such as cancer, atherosclerosis or fibrosis that are driven by abnormal expression of growth factors or their receptors.
硫酸乙酰肝素的复杂聚合结构包含硫酸化糖残基的链内序列，这些序列定义了生长因子结合和激活的活性位点。至少在硫酸乙酰肝素与碱性成纤维细胞生长因子相互作用的情况下，识别和激活的分子机制正在慢慢被揭示。目前的数据表明，硫酸乙酰肝素中相对较长但特定的结合序列可能会诱导碱性成纤维细胞生长因子的构象变化，从而暴露出蛋白质上一个被信号转导受体识别的位点。硫酸乙酰肝素还可能起到使碱性成纤维细胞生长因子二聚化以及通过与受体本身的二次相互作用促进受体转移的作用。已经提出了多种硫酸乙酰肝素介导碱性成纤维细胞生长因子诱导有丝分裂的模型，并且有迹象表明质膜硫酸乙酰肝素蛋白聚糖的核心蛋白可能参与细胞信号传导过程。硫酸乙酰肝素在控制生长因子活性方面的至关重要性为蛋白聚糖研究开启了新的篇章，并使蛋白聚糖进入了细胞生物学的主流。对其作用方式的进一步研究可能会揭示有关胚胎和成年组织中细胞生长和发育控制的新信息，并可能提出控制由生长因子或其受体异常表达驱动的疾病（如癌症、动脉粥样硬化或纤维化）的新方法。
