Fernig D G, Gallagher J T
Department of Biochemistry, University of Liverpool, U.K.
Prog Growth Factor Res. 1994;5(4):353-77. doi: 10.1016/0955-2235(94)00007-8.
The stimulation of cellular metabolism by the nine fibroblast growth factors (FGFs) is mediated by a dual-receptor system. This comprises a family of four receptor tyrosine kinases (FGFR) and heparan sulphate proteoglycans (HSPG). The stimulation of cell division by FGFs has an obligate requirement for both partners of the dual-receptor system. The binding of the nine FGFs to the FGFRs is marked by a pattern of overlapping specificity despite alternative splicing events generating a large number of FGFR proteins. Thus many of the FGFR isoforms bind several FGFs. It is likely that each FGF requires a different pattern of sulphation within the heparan sulphate chains for binding. Therefore, the HSPG receptors may provide additional specificity, allowing a cell to fine tune its response to the FGFs present in the extracellular milieu. The HSPG receptors also control the availability of FGFs and hence regulate the transport of FGFs within a tissue. FGF-stimulated cell division would appear to have a mandatory requirement for the FGFs to be translocated to the nucleus via the cytosol after interacting with the dual-receptor system. The consequences of the potential direct action of FGFs in stimulating cell division are examined in the light of current models of signal transduction.
九种成纤维细胞生长因子（FGFs）对细胞代谢的刺激作用是由一个双受体系统介导的。该系统由四种受体酪氨酸激酶（FGFR）家族和硫酸乙酰肝素蛋白聚糖（HSPG）组成。FGFs对细胞分裂的刺激作用对双受体系统的两个成员都有绝对需求。尽管选择性剪接事件产生了大量的FGFR蛋白，但九种FGFs与FGFRs的结合仍表现出重叠特异性模式。因此，许多FGFR异构体可结合几种FGFs。每种FGF可能需要硫酸乙酰肝素链内不同的硫酸化模式才能结合。因此，HSPG受体可能提供额外的特异性，使细胞能够微调其对细胞外环境中存在的FGFs的反应。HSPG受体还控制FGFs的可用性，从而调节FGFs在组织内的运输。FGF刺激的细胞分裂似乎绝对需要FGFs在与双受体系统相互作用后通过细胞质转运到细胞核。根据当前的信号转导模型，研究了FGFs在刺激细胞分裂中潜在直接作用的后果。
