Achieving Stability of Lipopolysaccharide-Induced NF-κB Activation
SciencePublished 15 September 2005
Markus W. Covert, Thomas Leung, Jahlionais E. Gaston, David Baltimore
Citations605
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
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-κB by the two pathways.
Abstract
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.
Keywords
Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology
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