Recurrent design patterns in the feedback regulation of the mammalian signalling network
Open Access
- 1 January 2008
- journal article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 4 (1), 190
- https://doi.org/10.1038/msb.2008.29
Abstract
Biochemical networks are characterized by recurrent patterns and motifs, but the design principles underlying the dynamics of the mammalian intracellular signalling network remain unclear. We systematically analysed decay rates of 134 signalling proteins and investigated their gene expression profiles in response to stimulation to get insights into transcriptional feedback regulation. We found a clear separation of the signalling pathways into flexible and static parts: for each pathway a subgroup of unstable signal inhibitors is transcriptionally induced upon stimulation, while the other constitutively expressed signalling proteins are long‐lived. Kinetic modelling suggests that this design principle allows for swift feedback regulation and establishes latency phases after signalling, and that it might be an optimal design due to a trade‐off between energy efficiency and flexibility.Keywords
This publication has 25 references indexed in Scilit:
- The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiaeScience, 2008
- Positioning of chemosensory clusters in E. coli and its relation to cell divisionThe EMBO Journal, 2007
- A module of negative feedback regulators defines growth factor signalingNature Genetics, 2007
- Specialization, Constraints, and Conflicting Interests in Mutualistic NetworksCurrent Biology, 2007
- Quantification of protein half-lives in the budding yeast proteomeProceedings of the National Academy of Sciences of the United States of America, 2006
- Noise in transcription negative feedback loops: simulation and experimental analysisMolecular Systems Biology, 2006
- Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK ResponsesPLoS Biology, 2005
- Principles behind the multifarious control of signal transductionThe FEBS Journal, 2004
- Control, exploitation and tolerance of intracellular noiseNature, 2002
- Hierarchies of ATP-consuming processes: direct compared with indirect measurements, and comparative aspectsBiochemical Journal, 2001