Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100 Israel.
Mol Cell. 2009 Dec 11;36(5):885-93. doi: 10.1016/j.molcel.2009.11.025.
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.
信号转导级联通常在细胞平均值上进行研究，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 的动态反应，ERK2 是一种特征明确的 MAPK 信号蛋白，在受到刺激后会进入细胞核。使用荧光标记在天然染色质基因座上，我们发现细胞在 ERK2 核水平上表现出广泛的基础变异。在 EGF 刺激下，细胞表现出（1）折叠变化反应，其中 ERK2 的核积累峰值与每个细胞的基础水平成正比；和（2）ERK2 核水平的精确适应，回到每个细胞的原始基础水平。ERK2 动力学的时间比其幅度在细胞之间更精确。我们进一步发现，在一些细胞中，ERK2 表现出第二次核进入的脉冲，小于第一次。本研究表明，这种信号系统补偿了自然生物噪声：尽管核基础水平存在很大差异，但 ERK2 的折叠动力学在细胞间相似。
