This is the distributive model described the article: Theoretical and experimental analysis links isoform-specific ERK signalling to cell fate decisions. Schilling M, Maiwald T, Hengl S, Winter D, Kreutz C, Kolch W, Lehmann WD, Timmer J and Klingmueller U; Mol Syst Biol. 2009;5:334. PubmedID: 20029368 ; DOI: 10.1038/msb.2009.91 Abstract: Cell fate decisions are regulated by the coordinated activation of signalling pathways such as the extracellular signal-regulated kinase (ERK) cascade, but contributions of individual kinase isoforms are mostly unknown. By combining quantitative data from erythropoietin-induced pathway activation in primary erythroid progenitor (colony-forming unit erythroid stage, CFU-E) cells with mathematical modelling, we predicted and experimentally confirmed a distributive ERK phosphorylation mechanism in CFU-E cells. Model analysis showed bow-tie-shaped signal processing and inherently transient signalling for cytokine-induced ERK signalling. Sensitivity analysis predicted that, through a feedback-mediated process, increasing one ERK isoform reduces activation of the other isoform, which was verified by protein over-expression. We calculated ERK activation for biochemically not addressable but physiologically relevant ligand concentrations showing that double-phosphorylated ERK1 attenuates proliferation beyond a certain activation level, whereas activated ERK2 enhances proliferation with saturation kinetics. Thus, we provide a quantitative link between earlier unobservable signalling dynamics and cell fate decisions. SBML model exported from PottersWheel on 2009-04-20 18:57:44. Below follows the source code for the model definition file in PottersWheel/Matlab: % PottersWheel model definition file function m = getModel() m = pwGetEmptyModel(); %% Meta information m.ID = 'ERK_distributive_model'; m.name = 'ERK_distributive_model'; m.description = 'ERK model calibrated to CFU-E as described in Schilling et al.'; m.authors = {'Marcel Schilling','Thomas Maiwald'}; m.dates = {'2009'}; m.type = 'PW-2-0'; %% Dynamic variables % m = pwAddX(m, ID, startValue, type, minValue, maxValue, unit, compartment, name, description, typeOfStartValue) m = pwAddX(m, 'JAK2' , 2, 'fix' , 1, 3.7, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'EpoR' , 1, 'fix' , 0.5, 1.5, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'SHP1' , 10.7991, 'global', 0.1, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'SOS' , 2.5101, 'fix' , 0.1, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Raf' , 3.7719, 'global', 0.1, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'MEK2' , 11, 'fix' , 8, 14, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'MEK1' , 24, 'fix' , 18, 30, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ERK1' , 7, 'global', 6, 9, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ERK2' , 21, 'fix' , 16, 26, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pJAK2' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pEpoR' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'mSHP1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'actSHP1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'mSOS' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pRaf' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ppMEK2' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ppMEK1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ppERK1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'ppERK2' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pSOS' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pMEK2' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pMEK1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pERK1' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'pERK2' , 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay01_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay02_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay03_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay04_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay05_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay06_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay07_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); m = pwAddX(m, 'Delay08_mSHP1', 0, 'fix' , 0, 100, [], 'cell', [] , [], 'concentration', [] ); %% Reactions % m = pwAddR(m, reactants, products, modifiers, type, options, rateSignature, parameters, description, ID, name, fast, compartments, parameterTrunks, designerProps) m = pwAddR(m, {'JAK2' }, {'pJAK2' }, {'Epo' }, 'E' , [] , [] , {'JAK2_phosphorylation_by_Epo' }, '...', 'reaction0001', [], [], {}, {}, {}); m = pwAddR(m, {'EpoR' }, {'pEpoR' }, {'pJAK2' }, 'E' , [] , [] , {'EpoR_phosphorylation_by_pJAK2' }, '...', 'reaction0002', [], [], {}, {}, {}); m = pwAddR(m, {'SHP1' }, {'mSHP1' }, {'pEpoR' }, 'E' , [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0003', [], [], {}, {}, {}); m = pwAddR(m, {'mSHP1' }, {'Delay01_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0004', [], [], {}, {}, {}); m = pwAddR(m, {'Delay01_mSHP1'}, {'Delay02_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0005', [], [], {}, {}, {}); m = pwAddR(m, {'Delay02_mSHP1'}, {'Delay03_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0006', [], [], {}, {}, {}); m = pwAddR(m, {'Delay03_mSHP1'}, {'Delay04_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0007', [], [], {}, {}, {}); m = pwAddR(m, {'Delay04_mSHP1'}, {'Delay05_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0008', [], [], {}, {}, {}); m = pwAddR(m, {'Delay05_mSHP1'}, {'Delay06_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0009', [], [], {}, {}, {}); m = pwAddR(m, {'Delay06_mSHP1'}, {'Delay07_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0010', [], [], {}, {}, {}); m = pwAddR(m, {'Delay07_mSHP1'}, {'Delay08_mSHP1'}, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0011', [], [], {}, {}, {}); m = pwAddR(m, {'Delay08_mSHP1'}, {'actSHP1' }, { }, 'MA', [] , [] , {'SHP1_activation_by_pEpoR' }, '...', 'reaction0012', [], [], {}, {}, {}); m = pwAddR(m, {'actSHP1' }, {'SHP1' }, { }, 'MA', [] , [] , {'actSHP1_deactivation' }, '...', 'reaction0005', [], [], {}, {}, {}); m = pwAddR(m, {'pEpoR' }, {'EpoR' }, {'actSHP1'}, 'E' , [] , [] , {'pEpoR_dephosphorylation_by_actSHP1' }, '...', 'reaction0006', [], [], {}, {}, {}); m = pwAddR(m, {'pJAK2' }, {'JAK2' }, {'actSHP1'}, 'E' , [] , [] , {'pJAK2_dephosphorylation_by_actSHP1' }, '...', 'reaction0007', [], [], {}, {}, {}); m = pwAddR(m, {'SOS' }, {'mSOS' }, {'pEpoR' }, 'E' , [] , [] , {'SOS_recruitment_by_pEpoR' }, '...', 'reaction0008', [], [], {}, {}, {}); m = pwAddR(m, {'mSOS' }, {'SOS' }, { }, 'MA', [] , [] , {'mSOS_release_from_membrane' }, '...', 'reaction0009', [], [], {}, {}, {}); m = pwAddR(m, {'Raf' }, {'pRaf' }, {'mSOS' }, 'E' , [] , [] , {'mSOS_induced_Raf_phosphorylation' }, '...', 'reaction0010', [], [], {}, {}, {}); m = pwAddR(m, {'pRaf' }, {'Raf' }, { }, 'MA', [] , [] , {'pRaf_dephosphorylation' }, '...', 'reaction0011', [], [], {}, {}, {}); m = pwAddR(m, {'MEK2' }, {'pMEK2' }, {'pRaf' }, 'E' , [] , [] , {'First_MEK2_phosphorylation_by_pRaf' }, '...', 'reaction0012', [], [], {}, {}, {}); m = pwAddR(m, {'MEK1' }, {'pMEK1' }, {'pRaf' }, 'E' , [] , [] , {'First_MEK1_phosphorylation_by_pRaf' }, '...', 'reaction0013', [], [], {}, {}, {}); m = pwAddR(m, {'pMEK2' }, {'ppMEK2' }, {'pRaf' }, 'E' , [] , [] , {'Second_MEK2_phosphorylation_by_pRaf' }, '...', 'reaction0014', [], [], {}, {}, {}); m = pwAddR(m, {'pMEK1' }, {'ppMEK1' }, {'pRaf' }, 'E' , [] , [] , {'Second_MEK1_phosphorylation_by_pRaf' }, '...', 'reaction0015', [], [], {}, {}, {}); m = pwAddR(m, {'ppMEK2' }, {'pMEK2' }, { }, 'MA', [] , [] , {'First_MEK_dephosphorylation' }, '...', 'reaction0016', [], [], {}, {}, {}); m = pwAddR(m, {'ppMEK1' }, {'pMEK1' }, { }, 'MA', [] , [] , {'First_MEK_dephosphorylation' }, '...', 'reaction0017', [], [], {}, {}, {}); m = pwAddR(m, {'pMEK2' }, {'MEK2' }, { }, 'MA', [] , [] , {'Second_MEK_dephosphorylation' }, '...', 'reaction0018', [], [], {}, {}, {}); m = pwAddR(m, {'pMEK1' }, {'MEK1' }, { }, 'MA', [] , [] , {'Second_MEK_dephosphorylation' }, '...', 'reaction0019', [], [], {}, {}, {}); m = pwAddR(m, {'ERK1' }, {'pERK1' }, {'ppMEK2' }, 'E' , [] , [] , {'First_ERK1_phosphorylation_by_ppMEK' }, '...', 'reaction0020', [], [], {}, {}, {}); m = pwAddR(m, {'ERK2' }, {'pERK2' }, {'ppMEK2' }, 'E' , [] , [] , {'First_ERK2_phosphorylation_by_ppMEK' }, '...', 'reaction0021', [], [], {}, {}, {}); m = pwAddR(m, {'ERK1' }, {'pERK1' }, {'ppMEK1' }, 'E' , [] , [] , {'First_ERK1_phosphorylation_by_ppMEK' }, '...', 'reaction0022', [], [], {}, {}, {}); m = pwAddR(m, {'ERK2' }, {'pERK2' }, {'ppMEK1' }, 'E' , [] , [] , {'First_ERK2_phosphorylation_by_ppMEK' }, '...', 'reaction0023', [], [], {}, {}, {}); m = pwAddR(m, {'pERK1' }, {'ppERK1' }, {'ppMEK2' }, 'E' , [] , [] , {'Second_ERK1_phosphorylation_by_ppMEK'}, '...', 'reaction0024', [], [], {}, {}, {}); m = pwAddR(m, {'pERK2' }, {'ppERK2' }, {'ppMEK2' }, 'E' , [] , [] , {'Second_ERK2_phosphorylation_by_ppMEK'}, '...', 'reaction0025', [], [], {}, {}, {}); m = pwAddR(m, {'pERK1' }, {'ppERK1' }, {'ppMEK1' }, 'E' , [] , [] , {'Second_ERK1_phosphorylation_by_ppMEK'}, '...', 'reaction0026', [], [], {}, {}, {}); m = pwAddR(m, {'pERK2' }, {'ppERK2' }, {'ppMEK1' }, 'E' , [] , [] , {'Second_ERK2_phosphorylation_by_ppMEK'}, '...', 'reaction0027', [], [], {}, {}, {}); m = pwAddR(m, {'ppERK1' }, {'pERK1' }, { }, 'MA', [] , [] , {'First_ERK_dephosphorylation' }, '...', 'reaction0028', [], [], {}, {}, {}); m = pwAddR(m, {'ppERK2' }, {'pERK2' }, { }, 'MA', [] , [] , {'First_ERK_dephosphorylation' }, '...', 'reaction0029', [], [], {}, {}, {}); m = pwAddR(m, {'pERK1' }, {'ERK1' }, { }, 'MA', [] , [] , {'Second_ERK_dephosphorylation' }, '...', 'reaction0030', [], [], {}, {}, {}); m = pwAddR(m, {'pERK2' }, {'ERK2' }, { }, 'MA', [] , [] , {'Second_ERK_dephosphorylation' }, '...', 'reaction0031', [], [], {}, {}, {}); m = pwAddR(m, {'mSOS' }, {'pSOS' }, {'ppERK1' }, 'E' , [] , [] , {'ppERK_neg_feedback_on_mSOS' }, '...', 'reaction0032', [], [], {}, {}, {}); m = pwAddR(m, {'mSOS' }, {'pSOS' }, {'ppERK2' }, 'E' , [] , [] , {'ppERK_neg_feedback_on_mSOS' }, '...', 'reaction0033', [], [], {}, {}, {}); m = pwAddR(m, {'pSOS' }, {'SOS' }, { }, 'MA', [] , [] , {'pSOS_dephosphorylation' }, '...', 'reaction0034', [], [], {}, {}, {}); %% Compartments % m = pwAddC(m, ID, size, outside, spatialDimensions, name, unit, constant) m = pwAddC(m, 'cell', 1, [], 3, 'cell', [], 1); %% Dynamical parameters % m = pwAddK(m, ID, value, type, minValue, maxValue, unit, name, description) m = pwAddK(m, 'JAK2_phosphorylation_by_Epo' , 0.0122149, 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'EpoR_phosphorylation_by_pJAK2' , 3.15714 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'SHP1_activation_by_pEpoR' , 0.408408 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'SHP1_delay' , 0.408408 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'actSHP1_deactivation' , 0.0248773, 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'pEpoR_dephosphorylation_by_actSHP1' , 1.19995 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'pJAK2_dephosphorylation_by_actSHP1' , 0.368384 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'SOS_recruitment_by_pEpoR' , 0.10271 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'mSOS_release_from_membrane' , 15.5956 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'mSOS_induced_Raf_phosphorylation' , 0.144515 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'pRaf_dephosphorylation' , 0.374228 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_MEK2_phosphorylation_by_pRaf' , 3.11919 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_MEK2_phosphorylation_by_pRaf' , 215.158 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_MEK1_phosphorylation_by_pRaf' , 0.687193 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_MEK1_phosphorylation_by_pRaf' , 667.957 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_MEK_dephosphorylation' , 0.130937 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_MEK_dephosphorylation' , 0.0732724, 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_ERK1_phosphorylation_by_ppMEK' , 2.4927 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_ERK1_phosphorylation_by_ppMEK', 59.5251 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_ERK2_phosphorylation_by_ppMEK' , 2.44361 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_ERK2_phosphorylation_by_ppMEK', 53.0816 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'First_ERK_dephosphorylation' , 39.0886 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'Second_ERK_dephosphorylation' , 3.00453 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'ppERK_neg_feedback_on_mSOS' , 5122.68 , 'fix', 1e-006, 10000, [], [], []); m = pwAddK(m, 'pSOS_dephosphorylation' , 0.124944 , 'fix', 1e-006, 10000, [], [], []); %% Default driving input % m = pwAddU(m, ID, uType, uTimes, uValues, compartment, name, description, u2Values) m = pwAddU(m, 'Epo', 'steps', [-60 0] , [0 50] , 'cell', [], [], [0 0]); %% Default sampling time points m.t = 0:1:35; %% Observables % m = pwAddY(m, rhs, ID, scalingParameter, errorModel, noiseType, unit, name, description) m = pwAddY(m, 'pEpoR' , 'pEpoR_obs' , 'scale_pEpoR_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'pJAK2' , 'pJAK2_obs' , 'scale_pJAK2_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'ppMEK2' , 'ppMEK2_obs', 'scale_ppMEK_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'ppMEK1' , 'ppMEK1_obs', 'scale_ppMEK_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'ppERK1' , 'ppERK1_obs', 'scale_ppERK_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'ppERK2' , 'ppERK2_obs', 'scale_ppERK_obs', 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'pSOS' , 'pSOS_obs' , 'scale_SOS_obs' , 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); m = pwAddY(m, 'SOS + mSOS', 'SOS_obs' , 'scale_SOS_obs' , 'y * 0.05 + max(y) * 0.05', 'Gaussian', [], [], []); %% Scaling parameters % m = pwAddS(m, ID, value, type, minValue, maxValue, unit, name, description) m = pwAddS(m, 'scale_pEpoR_obs', 0.493312, 'fix', 0.01, 50, [], [], []); m = pwAddS(m, 'scale_pJAK2_obs', 0.21008, 'fix', 0.01, 50, [], [], []); m = pwAddS(m, 'scale_ppMEK_obs', 40.5364, 'fix', 0.01, 50, [], [], []); m = pwAddS(m, 'scale_ppERK_obs', 13.5981, 'fix', 0.01, 50, [], [], []); m = pwAddS(m, 'scale_SOS_obs' , 1.10228, 'fix', 0.01, 50, [], [], []); %% Derived variables % m = pwAddZ(m, rhs, ID, unit, name, description) m = pwAddZ(m, 'ppERK1', 'ppERK1', [], [], []); m = pwAddZ(m, 'ppERK2', 'ppERK2', [], [], []); %% Derived parameters % m = pwAddP(m, rhs, ID, unit, name, description) %m = pwAddP(m, 'JAK2_phosphorylation_by_Epo'); %m = pwAddP(m, 'EpoR_phosphorylation_by_pJAK2'); %m = pwAddP(m, 'SHP1_activation_by_pEpoR'); %m = pwAddP(m, 'SHP1_delay'); %m = pwAddP(m, 'actSHP1_deactivation'); %m = pwAddP(m, 'pEpoR_dephosphorylation_by_actSHP1'); %m = pwAddP(m, 'pJAK2_dephosphorylation_by_actSHP1'); %m = pwAddP(m, 'SOS_recruitment_by_pEpoR'); %m = pwAddP(m, 'mSOS_release_from_membrane'); %m = pwAddP(m, 'mSOS_induced_Raf_phosphorylation'); %m = pwAddP(m, 'pRaf_dephosphorylation'); %m = pwAddP(m, 'First_MEK2_phosphorylation_by_pRaf'); %m = pwAddP(m, 'Second_MEK2_phosphorylation_by_pRaf'); %m = pwAddP(m, 'First_MEK1_phosphorylation_by_pRaf'); %m = pwAddP(m, 'Second_MEK1_phosphorylation_by_pRaf'); %m = pwAddP(m, 'First_MEK_dephosphorylation'); %m = pwAddP(m, 'Second_MEK_dephosphorylation'); %m = pwAddP(m, 'First_ERK1_phosphorylation_by_ppMEK'); %m = pwAddP(m, 'Second_ERK1_phosphorylation_by_ppMEK'); %m = pwAddP(m, 'First_ERK2_phosphorylation_by_ppMEK'); %m = pwAddP(m, 'Second_ERK2_phosphorylation_by_ppMEK'); %m = pwAddP(m, 'First_ERK_dephosphorylation'); %m = pwAddP(m, 'Second_ERK_dephosphorylation'); %m = pwAddP(m, 'ppERK_neg_feedback_on_mSOS'); %m = pwAddP(m, 'pSOS_dephosphorylation'); %m = pwAddP(m, 'JAK2'); %m = pwAddP(m, 'EpoR'); %m = pwAddP(m, 'SHP1'); %m = pwAddP(m, 'SOS'); %m = pwAddP(m, 'Raf'); %m = pwAddP(m, 'MEK2'); %m = pwAddP(m, 'MEK1'); %m = pwAddP(m, 'ERK1'); %m = pwAddP(m, 'ERK2'); %m = pwAddP(m, 'pJAK2'); %m = pwAddP(m, 'pEpoR'); %m = pwAddP(m, 'mSHP1'); %m = pwAddP(m, 'actSHP1'); %m = pwAddP(m, 'mSOS'); %m = pwAddP(m, 'pRaf'); %m = pwAddP(m, 'ppMEK2'); %m = pwAddP(m, 'ppMEK1'); %m = pwAddP(m, 'ppERK1'); %m = pwAddP(m, 'ppERK2'); %m = pwAddP(m, 'pSOS'); %m = pwAddP(m, 'pMEK2'); %m = pwAddP(m, 'pMEK1'); %m = pwAddP(m, 'pERK1'); %m = pwAddP(m, 'pERK2'); %m = pwAddP(m, 'Delay01_mSHP1'); %m = pwAddP(m, 'Delay02_mSHP1'); %m = pwAddP(m, 'Delay03_mSHP1'); %m = pwAddP(m, 'Delay04_mSHP1'); %m = pwAddP(m, 'Delay05_mSHP1'); %m = pwAddP(m, 'Delay06_mSHP1'); %m = pwAddP(m, 'Delay07_mSHP1'); %m = pwAddP(m, 'Delay08_mSHP1'); %m = pwAddP(m, 'scale_pEpoR_obs'); %m = pwAddP(m, 'scale_pJAK2_obs'); %m = pwAddP(m, 'scale_ppMEK_obs'); %m = pwAddP(m, 'scale_ppERK_obs'); %m = pwAddP(m, 'scale_SOS_obs'); %% Rules % m = pwAddRule(m, lhs, reactants, parameters, ruleSignature, type, description, ID) %% Constraints % m = pwAddConstraint(m, lhs, operator, rhs, reactants, parameters, lambda) m = pwAddConstraint(m, 'max(r1)/max(r2)', '=', '0.2', {'pERK1','ERK1'}, {}, 200); m = pwAddConstraint(m, 'max(r1)/max(r2)', '=', '0.2', {'pERK2','ERK2'}, {}, 200); m = pwAddConstraint(m, 'max(r1)/max(r2)', '=', '0.1', {'ppERK1','ERK1'}, {}, 200); m = pwAddConstraint(m, 'max(r1)/max(r2)', '=', '0.1', {'ppERK2','ERK2'}, {}, 200); This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels.net Team. For more information see the terms of use . 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.