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notes: This is a complex model to examine mechanisms that govern MAPK pathway dynamics in Chinese hamster ovary (CHO) cell lines, particularly the role of adapter targeted negative feedback mechanism in generating complete signal adaptation. This model simulates the results as per the figure 7A of the paper by Asthagiri AR and Lauffenburger DA. Biotechnol Prog. 17(2):227-39. 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.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
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notes: L CoInit = buffered at 0.03 uM from Asthagiri, A.R and Lauffenburger, D.A Biotechnol. Prog. 2001, 17, 227-239.
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notes: Kf12 and Kr12 are 3*10^8 M-1 min-1 and 0.5/sec from Asthagiri and 2001.
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notes: Implementation of adapter feedback induces adaptation of not only the target signal e0* but also signals downstream of the target. k5+ =6*10^8 M-1 min-1, k5- =30 min-1, kcat,5 =6 min-1 from Asthagiri and Lauffenburger 2001.
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501956
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notes: Kc12 and Kd12 are 3*10^8 M-1 min-1 and 0.5/sec from Asthagiri and 2001.
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notes: k4+ = 6*10^8 M-1 min-1, k4- =30 min-1, kcat,4 =6 min-1 from Asthagiri and 2001.
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reversible: true

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notes: k1*E4*E3_star_-k2*E3_star__slash_E4_activ_slash_E4_activ_cplx

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105595
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species: 650854

502551
type: SpeciesReference
stoichiometry: 1.0
species: 650934

651054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0427350427350427
initial amount: NaN
in compartment: 650414

651674
type: Reaction
kinetic law: 502975
product: 502962
reactant: 502949
reactant: 502937
notes: kp4+ = 6*10^8 M-1 min-1, kp4- =30 min-1, kpcat,4 =6 min-1 from Asthagiri and 2001.
fast: false
reversible: true

502975
type: KineticLaw
local parameters: 105613
local parameters: 105611
notes: k1*E4_star_*P4-k2*P4_slash_E4_star__deactiv_slash_E4_star__deactiv_cplx

105613
type: LocalParameter
units: 501639
value: 1.95E-13

105611
type: LocalParameter
units: 501676
value: 3.8999961E-12

502962
type: SpeciesReference
stoichiometry: 1.0
species: 651034

502949
type: SpeciesReference
stoichiometry: 1.0
species: 651014

651014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0213675213675214
initial amount: NaN
in compartment: 650414

502937
type: SpeciesReference
stoichiometry: 1.0
species: 650954

651694
type: Reaction
kinetic law: 503027
product: 503014
product: 503001
reactant: 502988
fast: false
reversible: false

503027
type: KineticLaw
local parameters: 105614
notes: k3*P4_slash_E4_star__deactiv_slash_E4_star__deactiv_cplx

105614
type: LocalParameter
units: 501639
value: 3.9E-14

503014
type: SpeciesReference
stoichiometry: 1.0
species: 651014

503001
type: SpeciesReference
stoichiometry: 1.0
species: 650934

502988
type: SpeciesReference
stoichiometry: 1.0
species: 651034

651174
type: Reaction
kinetic law: 501786
product: 501773
reactant: 501760
reactant: 501748
notes: Kf = 10^7/M-1 min-1 and Kr is 0.3 min-1 from Asthagiri, A.R and Lauffenburger, D.A Biotechnol. Prog. 2001, 227-239.
fast: false
reversible: true

501786
type: KineticLaw
local parameters: 105556
local parameters: 105554
notes: kf*L*R-kb*C

105556
type: LocalParameter
units: 501639
value: 1.95E-15

105554
type: LocalParameter
units: 501676
value: 6.49743822E-14

501773
type: SpeciesReference
stoichiometry: 1.0
species: 650454

501760
type: SpeciesReference
stoichiometry: 1.0
species: 650434

501748
type: SpeciesReference
stoichiometry: 1.0
species: 651154

651474
type: Reaction
kinetic law: 502490
product: 502478
reactant: 502466
reactant: 502454
notes: kp2+ =6*10^8 M-1 min-1, kp2- = 30 min-1, kpcat,2 = 6 min-1 from Asthagiri and 2001.
fast: false
reversible: true

502490
type: KineticLaw
local parameters: 105593
local parameters: 105591
notes: k1*E2_star_*P2-k2*P2_slash_E2_star__deactiv_slash_E2_star__deactiv_cplx

105593
type: LocalParameter
units: 501639
value: 1.95E-13

105591
type: LocalParameter
units: 501676
value: 3.8999961E-12

502478
type: SpeciesReference
stoichiometry: 1.0
species: 650814

502466
type: SpeciesReference
stoichiometry: 1.0
species: 650794

502454
type: SpeciesReference
stoichiometry: 1.0
species: 650754

651194
type: Reaction
kinetic law: 501822
product: 501810
reactant: 501798
notes: Kc is 6*10^7 M-1 min-1 and Ku is 60 min-1 from Asthagiri, A.R and Lauffenburger, D.A Biotechnol. Prog. 2001, 227-239.
fast: false
reversible: true

501822
type: KineticLaw
local parameters: 105559
local parameters: 105557
notes: kf*C^2-kb*C2

105559
type: LocalParameter
units: 501639
value: 3.9E-13

105557
type: LocalParameter
units: 501676
value: 3.8999961E-13

501810
type: SpeciesReference
stoichiometry: 1.0
species: 650494

501798
type: SpeciesReference
stoichiometry: 2.0
species: 650454

651454
type: Reaction
kinetic law: 502442
product: 502429
product: 502417
reactant: 502405
fast: false
reversible: false

502442
type: KineticLaw
local parameters: 105590
notes: k3*E2_star__slash_E3_activ_slash_E3_activ_cplx

105590
type: LocalParameter
units: 501639
value: 3.9E-14

502429
type: SpeciesReference
stoichiometry: 1.0
species: 650754

502417
type: SpeciesReference
stoichiometry: 1.0
species: 650854

502405
type: SpeciesReference
stoichiometry: 1.0
species: 650774

650401
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

651714
type: Reaction
kinetic law: 503078
product: 503066
reactant: 503053
reactant: 503040
notes: kp5+ = 6*10^8 M-1 min-1, kp5- = 30 min-1, kpcat,5 = 6 min-1 from Asthagiri and 2001.
fast: false
reversible: true

503078
type: KineticLaw
local parameters: 105617
local parameters: 105615
notes: k1*E5_star_*P5-k2*P5_slash_E5_star__deactiv_slash_E5_star__deactiv_cplx

105617
type: LocalParameter
units: 501639
value: 1.95E-13

105615
type: LocalParameter
units: 501676
value: 3.8999961E-12

503066
type: SpeciesReference
stoichiometry: 1.0
species: 651094

503053
type: SpeciesReference
stoichiometry: 1.0
species: 651074

503040
type: SpeciesReference
stoichiometry: 1.0
species: 651114

651734
type: Reaction
kinetic law: 503126
product: 503114
product: 503102
reactant: 503090
fast: false
reversible: false

503126
type: KineticLaw
local parameters: 105618
notes: k3*P5_slash_E5_star__deactiv_slash_E5_star__deactiv_cplx

105618
type: LocalParameter
units: 501639
value: 3.9E-14

503114
type: SpeciesReference
stoichiometry: 1.0
species: 651074

503102
type: SpeciesReference
stoichiometry: 1.0
species: 651054

503090
type: SpeciesReference
stoichiometry: 1.0
species: 651094

651594
type: Reaction
kinetic law: 502780
product: 502768
reactant: 502756
reactant: 502744
notes: k5+ =6*10^8 M-1 min-1, k5- =30 min-1, kcat,5 =6 min-1 from Asthagiri and 2001.
fast: false
reversible: true

502780
type: KineticLaw
local parameters: 105605
local parameters: 105603
notes: k1*E5*E4_star_-k2*E4_star__slash_E5_activ_slash_E5_activ_cplx

105605
type: LocalParameter
units: 501639
value: 1.95E-13

105603
type: LocalParameter
units: 501676
value: 3.8999961E-12

502768
type: SpeciesReference
stoichiometry: 1.0
species: 650974

502756
type: SpeciesReference
stoichiometry: 1.0
species: 650954

502744
type: SpeciesReference
stoichiometry: 1.0
species: 651054