Dynamics and Variability of ERK2 Response to EGF in Individual Living Cells

被引:182
作者
Cohen-Saidon, Cellina [1 ]
Cohen, Ariel A. [1 ]
Sigal, Alex [1 ]
Liron, Yuvalal [1 ]
Alon, Uri [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
关键词
ACTIVATED PROTEIN-KINASE; NUCLEAR TRANSLOCATION; GENE-EXPRESSION; MAP KINASE; PERFECT ADAPTATION; NEGATIVE-FEEDBACK; TYROSINE KINASE; PC12; CELLS; SIGNAL; RAS;
D O I
10.1016/j.molcel.2009.11.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:885 / 893
页数:9
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