ArticlePloS one2009
A dynamic analysis of IRS-PKR signaling in liver cells: a discrete modeling approach.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Insulin Signaling Pathway Model in Adipocyte Cells.Current pharmaceutical design · 2023Article
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- Understanding the mTOR signaling pathway via mathematical modeling.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.Frontiers in physiology · 2016Article
- Fanconi anemia cells with unrepaired DNA damage activate components of the checkpoint recovery process.Theoretical biology & medical modelling · 2015Article
- Normal vs. Malignant hematopoiesis: the complexity of acute leukemia through systems biology.Frontiers in genetics · 2015Article
- An integrative modeling framework reveals plasticity of TGF-β signaling.BMC systems biology · 2014Article
- Toward a systems-level view of dynamic phosphorylation networks.Frontiers in genetics · 2014Review
- Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells.BMC systems biology · 2013Article
- Logic-based models in systems biology: a predictive and parameter-free network analysis method.Integrative biology : quantitative biosciences from nano to macro · 2012Review
- A hierarchical whole-body modeling approach elucidates the link between in Vitro insulin signaling and in Vivo glucose homeostasis.The Journal of biological chemistry · 2011Article
- Simulating quantitative cellular responses using asynchronous threshold Boolean network ensembles.BMC systems biology · 2011Article
- Peroxisome proliferator-activated receptor agonist treatment of alcohol-induced hepatic insulin resistance.Hepatology research : the official journal of the Japan Society of Hepatology · 2011Article
- The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells.Molecular biology of the cell · 2010Article
- Logic-based models for the analysis of cell signaling networks.Biochemistry · 2010Review
- A dynamic analysis of IRS-PKR signaling in liver cells: a discrete modeling approach.PloS one · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A major challenge in systems biology is to develop a detailed dynamic understanding of the functions and behaviors in a particular cellular system, which depends on the elements and their inter-relationships in a specific network. Computational modeling plays an integral part in the study of network dynamics and uncovering the underlying mechanisms. Here we proposed a systematic approach that incorporates discrete dynamic modeling and experimental data to reconstruct a phenotype-specific network of cell signaling. A dynamic analysis of the insulin signaling system in liver cells provides a proof-of-concept application of the proposed methodology. Our group recently identified that double-stranded RNA-dependent protein kinase (PKR) plays an important role in the insulin signaling network. The dynamic behavior of the insulin signaling network is tuned by a variety of feedback pathways, many of which have the potential to cross talk with PKR. Given the complexity of insulin signaling, it is inefficient to experimentally test all possible interactions in the network to determine which pathways are functioning in our cell system. Our discrete dynamic model provides an in silico model framework that integrates potential interactions and assesses the contributions of the various interactions on the dynamic behavior of the signaling network. Simulations with the model generated testable hypothesis on the response of the network upon perturbation, which were experimentally evaluated to identify the pathways that function in our particular liver cell system. The modeling in combination with the experimental results enhanced our understanding of the insulin signaling dynamics and aided in generating a context-specific signaling network.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.