Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Montebello, 0379 Oslo, Norway.
Cells. 2021 May 28;10(6):1342. doi: 10.3390/cells10061342.
FGFR (fibroblast growth factor receptor) signaling controls fundamental processes in embryonic, fetal and adult human life. The magnitude, duration, and location of FGFR signaling must be strictly controlled in order to induce the correct biological response. Uncontrolled receptor signaling has been shown to lead to a variety of diseases, such as skeletal disorders and cancer. Here we review the numerous cellular mechanisms that regulate and turn off FGFR signaling, once the receptor is activated. These mechanisms include endocytosis and endocytic sorting, phosphatase activity, negative regulatory proteins and negative feedback phosphorylation events. The mechanisms act together simultaneously or sequentially, controlling the same or different steps in FGFR signaling. Although more work is needed to fully understand the regulation of FGFR signaling, it is clear that the cells in our body have evolved an extensive repertoire of mechanisms that together keep FGFR signaling tightly controlled and prevent excess FGFR signaling.
成纤维细胞生长因子受体 (FGFR) 信号通路控制着胚胎期、胎儿期和成人期人类生命的基本过程。为了诱导正确的生物学反应，FGFR 信号通路的强度、持续时间和位置必须受到严格控制。研究表明，不受控制的受体信号会导致多种疾病，如骨骼疾病和癌症。在这里，我们综述了许多细胞机制，这些机制在受体被激活后调节和关闭 FGFR 信号通路。这些机制包括内吞作用和内吞分选、磷酸酶活性、负调控蛋白和负反馈磷酸化事件。这些机制共同作用，或者先后作用，控制 FGFR 信号通路的相同或不同步骤。尽管还需要更多的工作来完全理解 FGFR 信号通路的调节，但很明显，我们体内的细胞已经进化出了广泛的机制，这些机制共同将 FGFR 信号通路严格控制，并防止 FGFR 信号通路过度激活。
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