Zhang Xiuqin, Ibrahimi Omar A, Olsen Shaun K, Umemori Hisashi, Mohammadi Moosa, Ornitz David M
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 2006 Jun 9;281(23):15694-700. doi: 10.1074/jbc.M601252200. Epub 2006 Apr 4.
In mammals, fibroblast growth factors (FGFs) are encoded by 22 genes. FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors (FGFRs 1-4). The spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans. In previous studies, we have engineered BaF3 cell lines to express the seven principal FGFRs and used these cell lines to determine the receptor binding specificity of FGFs 1-9 by using relative mitogenic activity as the readout. Here we have extended these semiquantitative studies to assess the receptor binding specificity of the remaining FGFs 10-23. This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity.
在哺乳动物中,成纤维细胞生长因子(FGFs)由22个基因编码。FGFs结合并激活四种酪氨酸激酶FGF受体(FGFRs 1 - 4)的可变剪接形式。FGFs和FGFRs的时空表达模式以及特定配体 - 受体对进行主动信号传导的能力是在各种生物学过程中调节FGF活性的重要因素。FGF信号活性受配体和受体的结合特异性调节,并受诸如硫酸乙酰肝素蛋白聚糖等外在辅助因子的调控。在先前的研究中,我们构建了表达七种主要FGFRs的BaF3细胞系,并使用这些细胞系以相对促有丝分裂活性作为读数来确定FGFs 1 - 9的受体结合特异性。在此,我们扩展了这些半定量研究,以评估其余FGFs 10 - 23的受体结合特异性。本研究完成了在标准条件下基于有丝分裂的整个FGF家族受体特异性比较,应有助于解释和预测体内生物学活性。