Dataset Information

TLR4-NFkB-phospho-NF-kB signaling in BMDM

ABSTRACT: The model was constructed to describe TLR4 induced NF-κB activation in native bone marrow-derived macrophages. It included processes of ligand (lipopolysaccharide) recognition, formation of dimer receptor complex and further signal transduction through TRAF6/TAK1 complex that leads to the activation of IKKα/β kinase, which in turn enables the NF-κB transcription factor phosphorylation and translocation in the cell nucleus, and induction of IkB and WIP1 (as an example of induced protein that promotes NF-κB dephosphorylation 2) gene transcription. Models were based on the current knowledge of TLR signaling framework, protein interactions within the TLR4 pathway, and up-to-date mathematical models describing Toll receptor activation. The major important additions were made to TLR4 signaling description: 1) Receptor dimerization process 2) The existence of a basal nuclear NF-κB level (translocation) 3) NF-κB phosphorylation by IKK complex

SUBMITTER: Alexander V Bagaev

PROVIDER: MODEL1809230001 | BioModels | 2019-03-27

REPOSITORIES: BioModels

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			Action	DRS
	MODEL1809230001?filename=TLR4-NF-kB_MACR_MODEL_SBML.xml	Xml

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Publications

Elevated pre-activation basal level of nuclear NF-κB in native macrophages accelerates LPS-induced translocation of cytosolic NF-κB into the cell nucleus.

Bagaev Alexander V AV Garaeva Anastasiya Y AY Lebedeva Ekaterina S ES Pichugin Alexey V AV Ataullakhanov Ravshan I RI Ataullakhanov Fazly I FI

Scientific reports 20190314 1

Signaling via Toll-like receptor 4 (TLR4) in macrophages constitutes an essential part of the innate immune response to bacterial infections. Detailed and quantified descriptions of TLR4 signal transduction would help to understand and exploit the first-line response of innate immune defense. To date, most mathematical modelling studies were performed on transformed cell lines. However, properties of primary macrophages differ significantly. We therefore studied TLR4-dependent activation of NF-κ ...[more]

PMID: 30872589

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