Rapraeger A C, Guimond S, Krufka A, Olwin B B
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, 53706, USA.
Methods Enzymol. 1994;245:219-40. doi: 10.1016/0076-6879(94)45013-7.
The integral role of heparan sulfate proteoglycans in FGF signaling provides a potential means of regulating FGF activity. This regulation may be used by the cell, where the modification of heparan sulfate glycosaminoglycans during their synthesis in the Golgi can produce cell type- and potentially ligand-specific sulfation sequences. The description of these sequences will not only provide information on how this regulation is achieved, perhaps lending insight into other heparan sulfate-ligand interactions, but may also discern sulfated mimetics that can be used to disrupt or alter FGF signaling. These mimetics may be useful in the treatment disrupt or alter FGF signaling. These mimetics may be useful in the treatment of disease, or in understanding how FGF signaling via discrete pathways within the cell leads to specific cellular responses, such as activation of mitogenic signaling pathways, calcium fluxes, and cellular differentiation.
硫酸乙酰肝素蛋白聚糖在成纤维细胞生长因子(FGF)信号传导中的不可或缺作用提供了一种调节FGF活性的潜在方式。细胞可能利用这种调节,因为在高尔基体中硫酸乙酰肝素糖胺聚糖合成过程中的修饰能够产生细胞类型特异性以及可能的配体特异性硫酸化序列。对这些序列的描述不仅将提供关于如何实现这种调节的信息,这或许有助于深入了解其他硫酸乙酰肝素-配体相互作用,而且还可能识别出可用于破坏或改变FGF信号传导的硫酸化模拟物。这些模拟物可能有助于疾病治疗,或者有助于理解细胞内通过离散途径的FGF信号传导如何导致特定的细胞反应,如促有丝分裂信号通路的激活、钙通量和细胞分化。