Achieving stability of lipopolysaccharide-induced NF-kappaB activation.

TitleAchieving stability of lipopolysaccharide-induced NF-kappaB activation.
Publication TypeJournal Article
Year of Publication2005
AuthorsCovert MW, Leung TH, Gaston JE, Baltimore D
Date Published2005 Sep 16
KeywordsAdaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Animals, Antigens, Differentiation, Cell Line, Cells, Cultured, Computer Simulation, Cycloheximide, DNA-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, I-kappa B Kinase, I-kappa B Proteins, Interferon Regulatory Factor-3, Kinetics, Lipopolysaccharides, Mice, Models, Biological, Myeloid Differentiation Factor 88, NF-kappa B, Oligonucleotide Array Sequence Analysis, Protein Synthesis Inhibitors, Protein-Serine-Threonine Kinases, Receptors, Immunologic, Signal Transduction, Time Factors, Toll-Like Receptor 4, Transcription Factors, Tumor Necrosis Factor-alpha

The activation dynamics of the transcription factor NF-kappaB exhibit damped oscillatory behavior when cells are stimulated by tumor necrosis factor-alpha (TNFalpha) but stable behavior when stimulated by lipopolysaccharide (LPS). LPS binding to Toll-like receptor 4 (TLR4) causes activation of NF-kappaB that requires two downstream pathways, each of which when isolated exhibits damped oscillatory behavior. Computational modeling of the two TLR4-dependent signaling pathways suggests that one pathway requires a time delay to establish early anti-phase activation of NF-kappaB by the two pathways. The MyD88-independent pathway required Inferon regulatory factor 3-dependent expression of TNFalpha to activate NF-kappaB, and the time required for TNFalpha synthesis established the delay.

PubMed URL
Alternate TitleScience
PubMed ID16166516