Please use this identifier to cite or link to this item: http://dx.doi.org/10.18419/opus-9232
Authors: Jensch, Antje
Thomaseth, Caterina
Radde, Nicole
Title: Sampling-based Bayesian approaches reveal the importance of quasi-bistable behavior in cellular decision processes on the example of the MAPK signaling pathway in PC-12 cell lines
Issue Date: 2017
metadata.ubs.publikation.typ: Zeitschriftenartikel
metadata.ubs.publikation.source: BMC systems biology 11 (2017), Nr. 11
URI: http://elib.uni-stuttgart.de/handle/11682/9249
http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-92492
http://dx.doi.org/10.18419/opus-9232
ISSN: 1752-0509
Abstract: Positive and negative feedback loops are ubiquitous motifs in biochemical signaling pathways. The mitogen-activated protein kinase (MAPK) pathway module is part of many distinct signaling networks and comprises several of these motifs, whose functioning depends on the cell line at hand and on the particular context. The maintainance of specificity of the response of the MAPK module to distinct stimuli has become a key paradigm especially in PC-12 cells, where the same module leads to different cell fates, depending on the stimulating growth factor. This cell fate is regulated by differences in the ERK (MAPK) activation profile, which shows a transient response upon stimulation with EGF, while the response is sustained in case of NGF. This behavior was explained by different effective network topologies. It is widely believed that this sustained response requires a bistable system. In this study we present a sampling-based Bayesian model analysis on a dataset, in which PC-12 cells have been stimulated with different growth factors. This is combined with novel analysis methods to investigate the role of feedback interconnections to shape ERK response. Results strongly suggest that, besides bistability, an additional effect called quasi-bistability can contribute to explain the observed responses of the system to different stimuli. Quasi-bistability is the ability of a monostable system to maintain two distinct states over a long time period upon a transient signal, which is also related to positive feedback, but cannot be detected by standard steady state analysis methods.
Appears in Collections:07 Fakultät Konstruktions-, Produktions- und Fahrzeugtechnik

Files in This Item:
File Description SizeFormat 
s12918-017-0392-6.pdfArticle2,62 MBAdobe PDFView/Open
s12918-017-0392-6_SI01.pdfAdditional file 1276,65 kBAdobe PDFView/Open
s12918-017-0392-6_SI02.pdfAdditional file 2131,71 kBAdobe PDFView/Open
s12918-017-0392-6_SI03.pdfAdditional file 3130,75 kBAdobe PDFView/Open
s12918-017-0392-6_SI04.pdfAdditional file 4137,96 kBAdobe PDFView/Open
s12918-017-0392-6_SI05.pdfAdditional file 564,59 kBAdobe PDFView/Open
s12918-017-0392-6_SI06.pdfAdditional file 68,67 MBAdobe PDFView/Open
s12918-017-0392-6_SI07.pdfAdditional file 7104,36 kBAdobe PDFView/Open
s12918-017-0392-6_SI08.pdfAdditional file 8175,84 kBAdobe PDFView/Open
s12918-017-0392-6_SI09.pdfAdditional file 951,96 kBAdobe PDFView/Open
s12918-017-0392-6_SI10.pdfAdditional file 1067,95 kBAdobe PDFView/Open


Items in OPUS are protected by copyright, with all rights reserved, unless otherwise indicated.