Theoretical and experimental analysis links isoform- specific ERK signalling to cell fate decisions
|Title:||Theoretical and experimental analysis links isoform- specific ERK signalling to cell fate decisions||Authors:||Schilling, Marcel
|Permanent link:||http://hdl.handle.net/10197/5052||Date:||22-Dec-2009||Online since:||2013-11-29T09:49:58Z||Abstract:||Cell fate decisions are regulated by the coordinated activation of signalling pathways such as the extracellular signal-regulated kinase (ERK) cascade, but contributions of individual kinase isoforms are mostly unknown. By combining quantitative data from erythropoietin-induced pathway activation in primary erythroid progenitor (colony-forming unit erythroid stage, CFU-E) cells with mathematical modelling, we predicted and experimentally confirmed a distributive ERK phosphorylation mechanism in CFU-E cells. Model analysis showed bow-tie-shaped signal processing and inherently transient signalling for cytokine-induced ERK signalling. Sensitivity analysis predicted that, through a feedback-mediated process, increasing one ERK isoform reduces activation of the other isoform, which was verified by protein over-expression. We calculated ERK activation for biochemically not addressable but physiologically relevant ligand concentrations showing that double-phosphorylated ERK1 attenuates proliferation beyond a certain activation level, whereas activated ERK2 enhances proliferation with saturation kinetics. Thus, we provide a quantitative link between earlier unobservable signalling dynamics and cell fate decisions.||Type of material:||Journal Article||Publisher:||Nature Publishing Group||Journal:||Molecular Systems Biology||Volume:||5||Issue:||334||Copyright (published version):||2009 Nature Publishing Group||Keywords:||endothelialization; coronary artery stents; restenosis; late stent thrombosis; liposome||DOI:||10.1038/msb.2009.91||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||SBI Research Collection|
Show full item record
Page view(s) 5037
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.