The JAK-STAT signaling network in the human B-cell: an extreme signaling pathway analysis.

TitleThe JAK-STAT signaling network in the human B-cell: an extreme signaling pathway analysis.
Publication TypeJournal Article
Year of Publication2004
AuthorsPapin JA, Palsson BO
JournalBiophys J
Date Published2004 Jul
KeywordsB-Lymphocytes, Computer Simulation, Cytokines, DNA-Binding Proteins, Humans, Protein Tyrosine Phosphatases, Signal Transduction, Systems Analysis, Trans-Activators

Large-scale models of signaling networks are beginning to be reconstructed and corresponding analysis frameworks are being developed. Herein, a reconstruction of the JAK-STAT signaling system in the human B-cell is described and a scalable framework for its network analysis is presented. This approach is called extreme signaling pathway analysis and involves the description of network properties with systemically independent basis vectors called extreme pathways. From the extreme signaling pathways, emergent systems properties of the JAK-STAT signaling network have been characterized, including 1), a mathematical definition of network crosstalk; 2), an analysis of redundancy in signaling inputs and outputs; 3), a study of reaction participation in the network; and 4), a delineation of 85 correlated reaction sets, or systemic signaling modules. This study is the first such analysis of an actual biological signaling system. Extreme signaling pathway analysis is a topologically based approach and assumes a balanced use of the signaling network. As large-scale reconstructions of signaling networks emerge, such scalable analyses will lead to a description of the fundamental systems properties of signal transduction networks.

PubMed URL
Alternate TitleBiophys. J.
PubMed ID15240442