English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Constraint-based modeling and kinetic analysis of the smad dependent TGF-ß signaling pathway

MPS-Authors
/persons/resource/persons50668

Zi,  Zhike
Cell Signaling Dynamics (Zhike Zi), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50384

Klipp,  Edda
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

Zi, Z., & Klipp, E. (2007). Constraint-based modeling and kinetic analysis of the smad dependent TGF-ß signaling pathway. PLoS One, 2(9), e936-e936. doi:10.1371/journal.pone.0000936.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-816B-4
Abstract
Background Investigation of dynamics and regulation of the TGF-β signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. Methodology/Principal Findings We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-β signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-β pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-β. Conclusions/Significance The simulation results indicate that the signal response to TGF-β is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.