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notes: This is the model described in the article: Stimulus specificity of gene expression programs determined by temporal control of IKK activity. by Werner SL, Barken D, Hoffmann A. Science. 2005 Sep 16;309(5742):1857-61; PMID: 16166517 , DOI= 10.1126/science.1113319 Abstract: A small number of mammalian signaling pathways mediate a myriad of distinct physiological responses to diverse cellular stimuli. Temporal control of the signaling module that contains IkappaB kinase (IKK), its substrate inhibitor of NF-kappaB (IkappaB), and the key inflammatory transcription factor NF-kappaB can allow for selective gene activation. We have demonstrated that different inflammatory stimuli induce distinct IKK profiles, and we examined the underlying molecular mechanisms. Although tumor necrosis factor-alpha (TNFalpha)-induced IKK activity was rapidly attenuated by negative feedback, lipopolysaccharide (LPS) signaling and LPS-specific gene expression programs were dependent on a cytokine-mediated positive feedback mechanism. Thus, the distinct biological responses to LPS and TNFalpha depend on signaling pathway-specific mechanisms that regulate the temporal profile of IKK activity. The model was implemented according to the description in the supplemental materials and by comparison to the matlab files provided by Prof. Hoffmann. It includes a delay for the induced transcription of IκBε mRNA. For the IKK input one of the randomly generated profiles was used. In its current form the model could not reproduce the time courses given in the article, as first the IKK activity profiles cannot easily be described by the same fitting functions in SBML and second the time delay limits simulation to tools, for which the current converters do not provide full SBML export. Originally created by libAntimony v1.4 (using libSBML 3.4.1) This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels…
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reversible: false
type: Reaction

868584
stoichiometry: 1.0
species: 058353
type: SpeciesReference

868889
stoichiometry: 1.0
species: 058356
type: SpeciesReference

869228
stoichiometry: 1.0
species: 058351
type: SpeciesReference

058568
constant: true
value: 6.0E-5
type: Parameter

058627
constant: true
value: 0.8
type: Parameter

869410
stoichiometry: 1.0
species: 058356
type: SpeciesReference

870221
stoichiometry: 1.0
species: 058363
type: SpeciesReference

058595
constant: true
value: 0.18
type: Parameter

868536
stoichiometry: 1.0
species: 058348
type: SpeciesReference

058606
constant: true
value: 0.36
type: Parameter

058530
constant: true
value: 15.0
type: Parameter

869508
stoichiometry: 1.0
species: 058353
type: SpeciesReference

058415
kinetic law: 869240
product: 869228
product: 869216
reactant: 869204
fast: false
reversible: false
type: Reaction

868077
stoichiometry: 1.0
species: 058358
type: SpeciesReference

058553
constant: true
value: 30.0
type: Parameter

058543
constant: true
value: 1.35
type: Parameter

868487
stoichiometry: 1.0
species: 058351
type: SpeciesReference

058582
constant: true
value: 0.012
type: Parameter

058626
constant: true
value: 7.92
type: Parameter

868680
stoichiometry: 1.0
species: 058362
type: SpeciesReference

058592
constant: true
value: 0.018
type: Parameter

058605
constant: true
value: 6.0E-5
type: Parameter

058542
constant: false
value: NaN
type: Parameter

868816
stoichiometry: 1.0
species: 058359
type: SpeciesReference

058406
kinetic law: 868853
product: 868841
product: 868828
reactant: 868816
fast: false
reversible: false
type: Reaction

869253
stoichiometry: 1.0
species: 058354
type: SpeciesReference

058552
constant: true
value: 11.1
type: Parameter

058583
constant: true
value: 0.012
type: Parameter

868548
stoichiometry: 1.0
species: 058353
type: SpeciesReference

058625
constant: true
value: 0.0168
type: Parameter

058593
constant: true
value: 5.4
type: Parameter

868572
stoichiometry: 1.0
species: 058356
type: SpeciesReference

058603
constant: true
value: 6.0E-5
type: Parameter

058369
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IκBε mRNA
type: Species

869520
stoichiometry: 1.0
species: 058354
type: SpeciesReference

870039
stoichiometry: 1.0
species: 058377
type: SpeciesReference

058379
kinetic law: 867821
product: 867809
reactant: 867797
reactant: 867785
fast: false
reversible: false
type: Reaction

868791
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058613
constant: true
value: 6.0E-5
type: Parameter

058399
kinetic law: 868608
product: 868596
product: 868584
reactant: 868572
fast: false
reversible: false
type: Reaction

869434
stoichiometry: 1.0
species: 058366
type: SpeciesReference

058389
kinetic law: 868214
product: 868202
reactant: 868189
reactant: 868177
fast: false
reversible: false
type: Reaction

058604
constant: true
value: 0.0012
type: Parameter

868427
stoichiometry: 1.0
species: 058363
type: SpeciesReference

869630
stoichiometry: 1.0
species: 058351
type: SpeciesReference

870391
stoichiometry: 1.0
species: 058369
type: SpeciesReference

058368
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IKKIκBβNF-κB
type: Species

867736
unit: 867748
name: micromole
type: SBMLUnitsDef

868475
stoichiometry: 1.0
species: 058372
type: SpeciesReference

870246
stoichiometry: 1.0
species: 058372
type: SpeciesReference

058570
constant: true
value: 0.075
type: Parameter

869337
stoichiometry: 1.0
species: 058371
type: SpeciesReference

058614
constant: true
value: 0.12
type: Parameter

870051
stoichiometry: 1.0
species: 058348
type: SpeciesReference

869955
stoichiometry: 1.0
species: 058348
type: SpeciesReference

058388
kinetic law: 868164
product: 868152
reactant: 868140
reactant: 868127
fast: false
reversible: false
type: Reaction

868937
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058550
constant: true
value: 30.0
type: Parameter

869398
stoichiometry: 1.0
species: 058357
type: SpeciesReference

867785
stoichiometry: 1.0
species: 058353
type: SpeciesReference

058398
kinetic law: 868560
product: 868548
product: 868536
reactant: 868524
fast: false
reversible: false
type: Reaction

869581
stoichiometry: 1.0
species: 058371
type: SpeciesReference

058367
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IKKIκBβ
type: Species

058601
constant: true
value: 6.0E-4
type: Parameter

868524
stoichiometry: 1.0
species: 058358
type: SpeciesReference

867978
stoichiometry: 1.0
species: 058371
type: SpeciesReference

058401
kinetic law: 868656
product: 868644
product: 868632
reactant: 868620
fast: false
reversible: false
type: Reaction

058615
constant: true
value: 0.18
type: Parameter

058387
kinetic law: 868115
product: 868102
reactant: 868090
reactant: 868077
fast: false
reversible: false
type: Reaction

867748
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

869059
stoichiometry: 1.0
species: 058377
type: SpeciesReference

870063
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058616
constant: true
value: 0.18
type: Parameter

868439
stoichiometry: 1.0
species: 058351
type: SpeciesReference

058402
kinetic law: 868704
product: 868692
product: 868680
reactant: 868668
fast: false
reversible: false
type: Reaction

058366
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058346
name: IκBβNF-κB nucleus
type: Species

869180
stoichiometry: 1.0
species: 058351
type: SpeciesReference

058386
kinetic law: 868064
product: 868051
reactant: 868038
reactant: 868026
fast: false
reversible: false
type: Reaction

868925
stoichiometry: 1.0
species: 058367
type: SpeciesReference

869967
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058575
constant: true
value: 0.105
type: Parameter

869544
stoichiometry: 1.0
species: 058362
type: SpeciesReference

058588
constant: true
value: 0.424
type: Parameter

868127
stoichiometry: 1.0
species: 058356
type: SpeciesReference

867772
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND
type: SBMLUnit

867809
stoichiometry: 1.0
species: 058358
type: SpeciesReference

870015
stoichiometry: 1.0
species: 058349
type: SpeciesReference

868728
stoichiometry: 1.0
species: 058348
type: SpeciesReference

869023
stoichiometry: 1.0
species: 058376
type: SpeciesReference

058364
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 058344
name: IκBβNF-κB
type: Species

058574
constant: true
value: 6.0E-5
type: Parameter

058610
constant: true
value: 6.0E-5
type: Parameter

058560
constant: true
value: 30.0
type: Parameter

058589
constant: true
value: 0.018
type: Parameter

869374
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058600
constant: true
value: 6.0E-5
type: Parameter

058374
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058346
name: IκBεNF-κB nucleus
type: Species

869919
stoichiometry: 1.0
species: 058349
type: SpeciesReference

868403
stoichiometry: 1.0
species: 058357
type: SpeciesReference

868451
stoichiometry: 1.0
species: 058366
type: SpeciesReference

058573
constant: true
value: 0.105
type: Parameter

058611
constant: true
value: 6.0E-5
type: Parameter

058363
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058346
name: IκBβ nucleus
type: Species

058377
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IKKIκBεNF-κB
type: Species

058563
constant: true
value: 6.0E-5
type: Parameter

868500
stoichiometry: 1.0
species: 058374
type: SpeciesReference

868716
stoichiometry: 1.0
species: 058376
type: SpeciesReference

870343
stoichiometry: 1.0
species: 058352
type: SpeciesReference

868391
stoichiometry: 1.0
species: 058351
type: SpeciesReference

058362
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IκBβ
type: Species

869907
stoichiometry: 1.0
species: 058373
type: SpeciesReference

869447
stoichiometry: 1.0
species: 058364
type: SpeciesReference

867797
stoichiometry: 1.0
species: 058348
type: SpeciesReference

058572
constant: true
value: 6.0E-5
type: Parameter

868102
stoichiometry: 1.0
species: 058359
type: SpeciesReference

058562
constant: true
value: 0.075
type: Parameter

869035
stoichiometry: 1.0
species: 058349
type: SpeciesReference

058376
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 058344
name: IKKIκBε
type: Species

870087
stoichiometry: 1.0
species: 058357
type: SpeciesReference

867953
stoichiometry: 1.0
species: 058364
type: SpeciesReference