UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling

Filippi, S; Barnes, CP; Kirk, PD; Kudo, T; Kunida, K; McMahon, SS; Tsuchiya, T; ... Stumpf, MP; + view all (2016) Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling. Cell Reports , 15 (11) pp. 2524-2535. 10.1016/j.celrep.2016.05.024. Green open access

[img]
Preview
Text
mmc2.pdf - Published version

Download (8MB) | Preview

Abstract

Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy) signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity.

Type: Article
Title: Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.05.024
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.05.024
Additional information: © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1497861
Downloads since deposit
76Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item