Automated FRET quantification shows distinct subcellular ERK activation kinetics in response to graded EGFR signaling in Drosophila
Automated FRET quantification shows distinct subcellular ERK activation kinetics in response to graded EGFR signaling in Drosophila
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DOI：
10.1111/gtc.12679
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发表时间：
2019-04-01
期刊：
影响因子：
2.1
通讯作者：
Hayashi, Shigeo
中科院分区：
文献类型：
--
作者：
Ogura, Yosuke;Sami, Mustafa M.;Hayashi, Shigeo
对活动梯度的阈值响应允许单个信号传导途径产生多种结果。细胞外信号调节激酶（ERK）就是这样一种信号，其将受体酪氨酸激酶信号传导与各种发育过程中的多种细胞反应偶联。最近的进展，在发展荧光生物传感器的活成像，使信号活动伴随胚胎发育被监测在真实的时间。在这里，我们使用了一个自动化的计算程序来量化的信号的荧光共振能量转移（FRET）报告激活ERK，我们用这个系统来监测时空动态的ERK在果蝇胚胎神经外胚层图案。我们发现，细胞质和细胞核ERK活性梯度显示不同的动力学响应表皮生长因子受体的激活。ERK的激活模式暗示细胞质ERK活性在细胞核中被调节成阈值反应。
Threshold responses to an activity gradient allow a single signaling pathway to yield multiple outcomes. Extracellular signal-regulated kinase (ERK) is one such signal, which couples receptor tyrosine kinase signaling with multiple cellular responses in various developmental processes. Recent advances in the development of fluorescent biosensors for live imaging have enabled the signaling activities accompanying embryonic development to be monitored in real time. Here, we used an automated computational program to quantify the signals of a fluorescence resonance energy transfer (FRET) reporter for activated ERK, and we used this system to monitor the spatio-temporal dynamics of ERK during neuroectoderm patterning in Drosophila embryos. We found that the cytoplasmic and nuclear ERK activity gradients show distinct kinetics in response to epidermal growth factor receptor activation. The ERK activation patterns implied that the cytoplasmic ERK activity is modulated into a threshold response in the nucleus.