Hecht D, Zimmerman N, Bedford M, Avivi A, Yayon A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Growth Factors. 1995;12(3):223-33. doi: 10.3109/08977199509036882.
Fibroblast growth factors (FGF) are multifunctional, heparin binding polypeptides that share structural similarity, but differ in their target cell specificity and expression pattern. Here we describe the cloning and expression of the mouse homologue of FGF9, and the use of a panel of soluble FGF receptors and genetically engineered cells to study its receptor binding specificity. FGF9 is found to bind with high affinity (kd: 0.25 nM) to FGFR3, for which a specific ligand has not yet been identified. FGF9 can also bind, albeit with a lower affinity, to FGFR2 but does not bind FGFR1 or FGFR4. There is no significant binding to either FGFR3 or FGFR2, expressed either as soluble receptors or in heparin sulfate deficient cells, in the absence of heparin. Moreover, receptor binding of FGF9 requires heparin in a manner specific to the receptor type. In conclusion FGF9 presents a unique case of ligand-receptor specificity and fulfills the criteria as a high affinity, heparin-dependent ligand for FGFR3.
成纤维细胞生长因子（FGF）是多功能的、与肝素结合的多肽，它们具有结构相似性，但在靶细胞特异性和表达模式上有所不同。在此，我们描述了FGF9小鼠同源物的克隆和表达，并利用一组可溶性FGF受体和基因工程细胞来研究其受体结合特异性。发现FGF9与FGFR3具有高亲和力结合（解离常数：0.25 nM），而FGFR3的特异性配体尚未确定。FGF9也能结合FGFR2，尽管亲和力较低，但不结合FGFR1或FGFR4。在没有肝素的情况下，无论是作为可溶性受体还是在硫酸乙酰肝素缺陷细胞中表达的FGFR3或FGFR2，都没有明显的结合。此外，FGF9的受体结合以受体类型特异性的方式需要肝素。总之，FGF9呈现出配体-受体特异性的独特情况，并满足作为FGFR3的高亲和力、肝素依赖性配体的标准。
