Dynamics and Variability of ERK2 Response to EGF in Individual Living Cells
Dynamics and Variability of ERK2 Response to EGF in Individual Living Cells
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DOI：
10.1016/j.molcel.2009.11.025
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发表时间：
2009-12-11
期刊：
影响因子：
16
通讯作者：
Alon, Uri
中科院分区：
文献类型：
--
作者：
Cohen-Saidon, Cellina;Cohen, Ariel A.;Alon, Uri
通常在细胞平均值上研究信号转移级联反应，从而掩盖了单个细胞之间的变异性。为了解决这个问题，我们在单个细胞中研究了ERK2的动态响应，ERK2是一种良好的MAPK信号蛋白，该蛋白在刺激后进入细胞核。使用内源性染色体基因座的荧光标记，我们发现细胞在ERK2核水平上显示出广泛的基础变化。 EGF刺激后，细胞显示（1）倍数变化反应，其中ERK2的峰值核积累与每个细胞中的基础水平成正比。 （2）ERK2的核水平的精确适应，返回每个细胞的原始基础水平。 ERK2动力学的时机在细胞之间比其振幅更精确。我们进一步发现，在某些细胞中，ERK2表现出第二个核进入脉冲，比第一个脉冲小。本研究表明，该信号系统补偿了自然的生物学噪声：尽管核基底水平发生较大，但ERK2的折叠动力学在细胞之间相似。
Signal-transduction cascades are usually studied on cell averages, masking variability between individual cells. To address this, we studied in individual cells the dynamic response of ERK2, a well-characterized MAPK signaling protein, which enters the nucleus upon stimulation. Using fluorescent tagging at the endogenous chromosomal locus, we found that cells show wide basal variation in ERK2 nuclear levels. Upon EGF stimulation, cells show (1) a fold-change response, where peak nuclear accumulation of ERK2 is proportional to basal level in each cell; and (2) exact adaptation in nuclear levels of ERK2, returning to original basal level of each cell. The timing of ERK2 dynamics is more precise between cells than its amplitude. We further found that in some cells ERK2 exhibits a second pulse of nuclear entry, smaller than the first. The present study suggests that this signaling system compensates for natural biological noise: despite large variation in nuclear basal levels, ERK2's fold dynamics is similar between cells.