Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.
Exp Cell Res. 2011 Apr 15;317(7):1005-15. doi: 10.1016/j.yexcr.2011.01.003. Epub 2011 Jan 8.
Fibroblast growth factor 1 (FGF1) has the property to become translocated from the extracellular space into the cell cytosol and nucleus. Membrane translocation of FGF1 occurs subsequent to endocytic uptake and is strictly FGF-receptor (FGFR) dependent. Here we have investigated the timing of FGF1 translocation in relation to FGFR1 signalling. We found that the translocation of FGF1 is a periodic event that occurs with 24h intervals. Serum-starved cells translocated the growth factor with peak occurrences ~6 h, ~30 h, and ~54 h after the addition of FGF1. The periodic FGF1 translocation was totally independent of the FGFR1 tyrosine kinase activity as it proceeded unchanged when the kinase activity was chemically inhibited or the kinase domain was deleted. Furthermore, FGF1 translocation was not restricted to a particular phase of the cell cycle or dependent on cell cycle progression. The results demonstrate that the FGF1/FGFR1 complex constitutes a signalling module that independently of the receptor tyrosine kinase can convey a signal that initiates a strictly timed and periodic release of endocytosed FGF1 into the cytosol/nucleus.
成纤维细胞生长因子 1（FGF1）具有从细胞外空间转位到细胞质和细胞核的特性。FGF1 的膜转位发生在细胞内吞作用之后，并且严格依赖于成纤维细胞生长因子受体（FGFR）。在这里，我们研究了 FGF1 转位与 FGFR1 信号转导的时间关系。我们发现 FGF1 的转位是一个周期性事件，每隔 24 小时发生一次。在添加 FGF1 后 6 小时、30 小时和 54 小时左右，血清饥饿的细胞转位生长因子的峰值出现。周期性 FGF1 转位完全独立于 FGFR1 酪氨酸激酶活性，因为当激酶活性被化学抑制或激酶结构域被删除时，它没有改变。此外，FGF1 转位不受细胞周期特定阶段的限制，也不依赖于细胞周期的进展。结果表明，FGF1/FGFR1 复合物构成了一个信号模块，它可以独立于受体酪氨酸激酶传递信号，启动内吞 FGF1 严格定时和周期性释放到细胞质/核。
