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BIOMD0000000410 - Wegner2012_TGFbetaSignalling_FeedbackLoops

 

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Reference Publication
Publication ID: 22284904
Wegner K, Bachmann A, Schad JU, Lucarelli P, Sahle S, Nickel P, Meyer C, Klingmüller U, Dooley S, Kummer U.
Dynamics and feedback loops in the transforming growth factor β signaling pathway.
Biophys. Chem. 2012 Mar; 162: 22-34
Biological and Neural Computation Group, Science and Technology Research Institute, University of Hertfordshire, College Lane, Hatfield, United Kingdom. wegner@dhbw-karlsruhe.de  [more]
Model
Original Model: BIOMD0000000410.origin
Submitter: Katja Wengler (neé Wegner)
Submission ID: MODEL1202090000
Submission Date: 09 Feb 2012 07:56:00 UTC
Last Modification Date: 27 Mar 2012 13:41:12 UTC
Creation Date: 10 Feb 2012 11:45:56 UTC
Encoders:  Vijayalakshmi Chelliah
   Katja Wegner
   Anastasia Bachmann
set #1
bqbiol:isVersionOf Gene Ontology transforming growth factor beta receptor signaling pathway
bqbiol:occursIn Taxonomy Mus musculus
Brenda Tissue Ontology hepatocyte
Notes

This model is from the article:
Dynamics and feedback loops in the transforming growth factor β signaling pathway.
Wegner K, Bachmann A, Schad JU, Lucarelli P, Sahle S, Nickel P, Meyer C, Klingmüller U, Dooley S, Kummer U. Biophys Chem. 2012 Jan 5. 22284904 ,
Abstract:
Transforming growth factor β (TGF-β) ligands activate a signaling cascade with multiple cell context dependent outcomes. Disruption or disturbance leads to variant clinical disorders. To develop strategies for disease intervention, delineation of the pathway in further detail is required. Current theoretical models of this pathway describe production and degradation of signal mediating proteins and signal transduction from the cell surface into the nucleus, whereas feedback loops have not exhaustively been included. In this study we present a mathematical model to determine the relevance of feedback regulators (Arkadia, Smad7, Smurf1, Smurf2, SnoN and Ski) on TGF-β target gene expression and the potential to initiate stable oscillations within a realistic parameter space. We employed massive sampling of the parameters space to pinpoint crucial players for potential oscillations as well as transcriptional product levels. We identified Smad7 and Smurf2 with the highest impact on the dynamics. Based on these findings, we conducted preliminary time course experiments.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 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.

Model
Publication ID: 22284904 Submission Date: 09 Feb 2012 07:56:00 UTC Last Modification Date: 27 Mar 2012 13:41:12 UTC Creation Date: 10 Feb 2012 11:45:56 UTC
Mathematical expressions
Reactions
Smad_dissoc3 Smad2_dephosphNuc Smad_inhibComp2SnoN SnoN_degrad2
Smad_compNuc2 Smad2_dephosphNuc2 Smad2_degrad Smad7-Smurf2
Rec_comp1 Rec_comp2 SARA-comp2 Smad2_phosph
Smad2_phosphSARA Smad2-P_transp Smad_compCyt2 Smad4_transp
Smad_compTransp2 Smad7_transp Smad7-Smurf2_transp Rec_degrad1
Rec_inhib fluxRecII fluxSara fluxSmad7
fluxSmurf2 fluxSnoN fluxRecI Smad4-SnoN
Smad2_transp Rec_degrad RecI_degrad RecII_degrad
Rec_recycl fluxSmad2 fluxSmad4 Smad4_degrad
SARA_degrad Smad2_dephospCyt SnoN_degrad Smurf2_transp
Smad2_cyt_degrad SnoN_trans fluxSmad3 Smad3_cyt_degrad
Smad3_dephospCyt Smad3_dephospNuc Smad3_dephospNuc2 Smad3_phosph
Smad3_phosphSARA Smad3_degrad Smad3_transp SARA-comp3
Smad_dissoc2 Smad3-P-transp Smad_compCyt3 Smad_compNuc3
Smad_inhibComp3SnoN Smad_compTransp3 SnoN_degrad3 Smad7_degrad
Ski_degrad Ski_trans fluxSki Smurf2_degrad
Smad4-Ski Smad3-Ski_cyt Smad7-Smurf1 fluxSmurf1
Smad_inhibComp3Ski Rec_degrad2 Smad7-Smurf1_transp Smurf1_degrad
Smurf1_transp Smad3-freePromot Smad2-freePromot Smad3-SnoN-freePromot
Smad2-SnoN-gene Smad3-Ski-freePromot Smad_inhibComp2Ski Smad2-Ski-gene
Smad4-freePromot Smad2-Ski_cyt Smad2-Snon Smad3-Snon
Smad2-comp-degrad Samd3-comp-degrad fluxArkadia Arkadia_deg
SnoN-deg2 SnoN-deg3 transArkadia  
Rules
Assignment Rule (variable: allSmad7) Assignment Rule (variable: allSnoN) Assignment Rule (variable: allSmurf2) Assignment Rule (variable: allSmad2)
Assignment Rule (variable: allSmad4) Assignment Rule (variable: allPSmad3) Assignment Rule (variable: allSmad3) Assignment Rule (variable: allSmad4cyt)
Assignment Rule (variable: allSmad4nuc)      
Physical entities
Compartments Species
cytoplasm TGF_RII TGFbeta_TGF_RII TGF_RI
Rec_active Smad2_c SARA
Smad2_SARA pSmad2_c Smad4_c
pSmad2_Smad4_c Smad7_c Smad7_Smurf2_c
Rec_Smad7 Smurf2_c SnoN_c
Smad3_c pSmad3_c Smad3_SARA
pSmad3_Smad4_c Ski_c Smad3_Ski_c
Smurf1_c Smad7_Smurf1_c pSmad2_Smad4_Ski_n
Smad2_Ski_c pSmad2_SnoN_n pSmad3_SnoN_n
Arkadia_c    
nucleus Smad4_n pSmad2_Smad4_n SnoN_n
pSmad2_Smad4_SnoN_n Smurf2_n pSmad2_n
Smad2_n Smad7_n Smad7_Smurf2_n
Smad4_SnoN_n Smad3_n pSmad3_Smad4_n
Smad4_Smad2_n pSmad3_n pSmad3_Smad4_SnoN_n
Ski_n Smad4_Ski_n Smurf1_n
Smad7_Smurf1_n pSmad3_Smad4_Ski_n Smad4_Smad3_n
freePromoters inactivePromoters geneProduct
Arkadia_n    
Global parameters
TGFbeta allSnoN allSmad7 allSmurf2
allSmad2 allSmad4 allPSmad3 allSmad3
allSmad4cyt allSmad4nuc    
Reactions (91)
 
 Smad_dissoc3 [Smad4_Smad3_n] → [Smad4_n] + 2.0 × [Smad3_n];  
 
 Smad2_dephosphNuc [pSmad2_Smad4_n] → [Smad4_Smad2_n];  
 
 Smad_inhibComp2SnoN [pSmad2_Smad4_n] + 2.0 × [SnoN_n] ↔ [pSmad2_Smad4_SnoN_n];  
 
 SnoN_degrad2 3.0 × [Smurf2_n] + [pSmad2_SnoN_n] → 3.0 × [pSmad2_n];  
 
 Smad_compNuc2 [Smad4_n] + 2.0 × [pSmad2_n] → [pSmad2_Smad4_n];  
 
 Smad2_dephosphNuc2 [pSmad2_n] → [Smad2_n];  
 
 Smad2_degrad [Smad2_n] + [Smurf2_n] → ;  
 
 Smad7-Smurf2 [Smurf2_n] + [Smad7_n] ↔ [Smad7_Smurf2_n];  
 
 Rec_comp1 2.0 × [TGF_RII] → [TGFbeta_TGF_RII];   {TGF_RII}
 
 Rec_comp2 [TGFbeta_TGF_RII] + 2.0 × [TGF_RI] ↔ [Rec_active];  
 
 SARA-comp2 [SARA] + [Smad2_c] ↔ [Smad2_SARA];  
 
 Smad2_phosph [Smad2_c] → [pSmad2_c];   {Rec_active}
 
 Smad2_phosphSARA [Smad2_SARA] → [pSmad2_c] + [SARA];   {Rec_active}
 
 Smad2-P_transp [pSmad2_c] → [pSmad2_n];  
 
 Smad_compCyt2 [Smad4_c] + 2.0 × [pSmad2_c] → [pSmad2_Smad4_c];  
 
 Smad4_transp [Smad4_c] ↔ [Smad4_n];  
 
 Smad_compTransp2 [pSmad2_Smad4_c] → [pSmad2_Smad4_n];  
 
 Smad7_transp [Smad7_n] ↔ [Smad7_c];  
 
 Smad7-Smurf2_transp [Smad7_Smurf2_n] ↔ [Smad7_Smurf2_c];  
 
 Rec_degrad1 [Smad7_Smurf2_c] + [Rec_active] → ;  
 
 Rec_inhib [Smad7_c] + [Rec_active] ↔ [Rec_Smad7];  
 
 fluxRecII  → [TGF_RII];  
 
 fluxSara  → [SARA];   {geneProduct}
 
 fluxSmad7  → [Smad7_c];   {geneProduct} , {Smad4_SnoN_n} , {Smad4_Ski_n}
 
 fluxSmurf2  → [Smurf2_c];   {geneProduct}
 
 fluxSnoN  → [SnoN_c];   {geneProduct}
 
 fluxRecI  → [TGF_RI];  
 
 Smad4-SnoN [Smad4_n] + [SnoN_n] ↔ [Smad4_SnoN_n];  
 
 Smad2_transp [Smad2_c] ↔ [Smad2_n];  
 
 Rec_degrad [Rec_active] → ;  
 
 RecI_degrad [TGF_RI] → ;  
 
 RecII_degrad [TGF_RII] → ;  
 
 Rec_recycl [TGFbeta_TGF_RII] → 2.0 × [TGF_RII];  
 
 fluxSmad2  → [Smad2_c];  
 
 fluxSmad4  → [Smad4_c];  
 
 Smad4_degrad [Smad4_c] → ;  
 
 SARA_degrad [SARA] → ;  
 
 Smad2_dephospCyt [pSmad2_c] → [Smad2_c];  
 
 SnoN_degrad [SnoN_c] → ;  
 
 Smurf2_transp [Smurf2_n] ↔ [Smurf2_c];  
 
 Smad2_cyt_degrad [Smad2_c] → ;  
 
 SnoN_trans [SnoN_c] ↔ [SnoN_n];  
 
 fluxSmad3  → [Smad3_c];  
 
 Smad3_cyt_degrad [Smad3_c] → ;  
 
 Smad3_dephospCyt [pSmad3_c] → [Smad3_c];  
 
 Smad3_dephospNuc [pSmad3_Smad4_n] → [Smad4_Smad3_n];  
 
 Smad3_dephospNuc2 [pSmad3_n] → [Smad3_n];  
 
 Smad3_phosph [Smad3_c] → [pSmad3_c];   {Rec_active}
 
 Smad3_phosphSARA [Smad3_SARA] → [pSmad3_c] + [SARA];   {Rec_active}
 
 Smad3_degrad [Smad3_n] → ;  
 
 Smad3_transp [Smad3_c] ↔ [Smad3_n];  
 
 SARA-comp3 [SARA] + [Smad3_c] ↔ [Smad3_SARA];  
 
 Smad_dissoc2 [Smad4_Smad2_n] → [Smad4_n] + 2.0 × [Smad2_n];  
 
 Smad3-P-transp [pSmad3_c] → [pSmad3_n];  
 
 Smad_compCyt3 [Smad4_c] + 2.0 × [pSmad3_c] → [pSmad3_Smad4_c];  
 
 Smad_compNuc3 [Smad4_n] + 2.0 × [pSmad3_n] → [pSmad3_Smad4_n];  
 
 Smad_inhibComp3SnoN [pSmad3_Smad4_n] + 2.0 × [SnoN_n] ↔ [pSmad3_Smad4_SnoN_n];  
 
 Smad_compTransp3 [pSmad3_Smad4_c] → [pSmad3_Smad4_n];  
 
 SnoN_degrad3 [pSmad3_SnoN_n] → [pSmad3_n];  
 
 Smad7_degrad [Smad7_c] → ;   {Arkadia_c}
 
 Ski_degrad [Ski_c] → ;  
 
 Ski_trans [Ski_c] ↔ [Ski_n];  
 
 fluxSki  → [Ski_c];   {geneProduct}
 
 Smurf2_degrad [Smurf2_c] → ;   {Smad7_c}
 
 Smad4-Ski [Smad4_n] + [Ski_n] ↔ [Smad4_Ski_n];  
 
 Smad3-Ski_cyt [Smad3_c] + [Ski_c] ↔ [Smad3_Ski_c];  
 
 Smad7-Smurf1 [Smurf1_n] + [Smad7_n] ↔ [Smad7_Smurf1_n];  
 
 fluxSmurf1  → [Smurf1_c];   {geneProduct}
 
 Smad_inhibComp3Ski [pSmad3_Smad4_n] + 2.0 × [Ski_n] ↔ [pSmad3_Smad4_Ski_n];  
 
 Rec_degrad2 [Smad7_Smurf1_c] + [Rec_active] → ;  
 
 Smad7-Smurf1_transp [Smad7_Smurf1_n] ↔ [Smad7_Smurf1_c];  
 
 Smurf1_degrad [Smurf1_c] → ;   {Smad7_c}
 
 Smurf1_transp [Smurf1_n] ↔ [Smurf1_c];  
 
 Smad3-freePromot [pSmad3_Smad4_n] + [freePromoters] ↔ [geneProduct];  
 
 Smad2-freePromot [pSmad2_Smad4_n] + [freePromoters] ↔ [geneProduct];  
 
 Smad3-SnoN-freePromot [pSmad3_Smad4_SnoN_n] + [freePromoters] ↔ [inactivePromoters];  
 
 Smad2-SnoN-gene [pSmad2_Smad4_SnoN_n] + [freePromoters] ↔ [inactivePromoters];  
 
 Smad3-Ski-freePromot [pSmad3_Smad4_Ski_n] + [freePromoters] ↔ [inactivePromoters];  
 
 Smad_inhibComp2Ski [pSmad2_Smad4_n] + 2.0 × [Ski_n] ↔ [pSmad2_Smad4_Ski_n];  
 
 Smad2-Ski-gene [pSmad2_Smad4_Ski_n] + [freePromoters] ↔ [inactivePromoters];  
 
 Smad4-freePromot [Smad4_Ski_n] + [freePromoters] ↔ [inactivePromoters];  
 
 Smad2-Ski_cyt [Smad2_c] + [Ski_c] ↔ [Smad2_Ski_c];  
 
 Smad2-Snon 3.0 × [pSmad2_n] + 3.0 × [SnoN_n] ↔ [pSmad2_SnoN_n];  
 
 Smad3-Snon 3.0 × [pSmad3_n] + 3.0 × [SnoN_n] ↔ [pSmad3_SnoN_n];  
 
 Smad2-comp-degrad [pSmad2_Smad4_n] → ;  
 
 Samd3-comp-degrad [pSmad3_Smad4_n] → ;  
 
 fluxArkadia  → [Arkadia_c];  
 
 Arkadia_deg [Arkadia_c] → ;  
 
 SnoN-deg2 [pSmad2_SnoN_n] + 3.0 × [Arkadia_n] → 3.0 × [pSmad2_n];  
 
 SnoN-deg3 [pSmad3_SnoN_n] + 3.0 × [Arkadia_n] → [pSmad3_n];  
 
 transArkadia [Arkadia_c] ↔ [Arkadia_n];  
 
Rules (9)
 
 Assignment Rule (name: parameter_3) allSmad7 = _174+_181+_198+_25+_27
 
 Assignment Rule (name: parameter_2) allSnoN = species_2+_11+species_16+species_16
 
 Assignment Rule (name: parameter_4) allSmurf2 = _181+species_1+_15+_27
 
 Assignment Rule (name: parameter_5) allSmad2 = _99+_105+_129+_153+_9+_13+_19+_21+species_19
 
 Assignment Rule (name: parameter_6) allSmad4 = _147+_153+species_6+_5+_9+species_18+_13+species_16+species_19+species_21+species_27+species_26+species_23
 
 Assignment Rule (name: parameter_7) allPSmad3 = species_4+species_6+species_18+species_20+species_21+species_26
 
 Assignment Rule (name: parameter_8) allSmad3 = species_3+species_4+species_5+species_6+species_8+species_17+species_18+species_20+species_21+species_26+species_27
 
 Assignment Rule (name: parameter_9) allSmad4cyt = _147+_153+species_6
 
 Assignment Rule (name: parameter_10) allSmad4nuc = species_11+_5+_9+_13+species_18+species_16+species_18+species_19+species_21+species_23+species_26+species_26+species_27
 
Functions (7)
 
 Constant flux (irreversible) lambda(v, v)
 
 Henri-Michaelis-Menten (irreversible) lambda(substrate, Km, V, V*substrate/(Km+substrate))
 
 Rate Law for SARA-Phosph [1] lambda(k, rec, s, km, k*rec*s/(km+s))
 
 Rate Law for Rec_comp1 [1] lambda(TGFbeta, k, s, s2, k*s*s2*TGFbeta)
 
 Rate Law for Degradation lambda(k1, substrate, modifier, k1*substrate*(1+modifier))
 
 Rate Law for flux and basicflux [1] lambda(k, k1, m, k+k1*m)
 
 Rate Law for fluxSmad7_1 [1] lambda(k, k1, m, m2, m3, (k+k1*m)/(1+m2+m3))
 
 cytoplasm Spatial dimensions: 3.0  Compartment size: 1.0
 
 TGF_RII
Compartment: cytoplasm
Initial concentration: 0.0
 
 TGFbeta_TGF_RII
Compartment: cytoplasm
Initial concentration: 0.0
 
 TGF_RI
Compartment: cytoplasm
Initial concentration: 0.0
 
 Rec_active
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad2_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 SARA
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad2_SARA
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad2_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad4_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad2_Smad4_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad7_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad7_Smurf2_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Rec_Smad7
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smurf2_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 SnoN_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad3_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad3_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad3_SARA
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad3_Smad4_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Ski_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad3_Ski_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smurf1_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad7_Smurf1_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad2_Smad4_Ski_n
Compartment: cytoplasm
Initial concentration: 0.0
 
 Smad2_Ski_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad2_SnoN_n
Compartment: cytoplasm
Initial concentration: 0.0
 
 pSmad3_SnoN_n
Compartment: cytoplasm
Initial concentration: 0.0
 
 Arkadia_c
Compartment: cytoplasm
Initial concentration: 0.0
 
 nucleus Spatial dimensions: 3.0  Compartment size: 1.0
 
 Smad4_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad2_Smad4_n
Compartment: nucleus
Initial concentration: 0.0
 
 SnoN_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad2_Smad4_SnoN_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smurf2_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad2_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad2_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad7_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad7_Smurf2_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad4_SnoN_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad3_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad3_Smad4_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad4_Smad2_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad3_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad3_Smad4_SnoN_n
Compartment: nucleus
Initial concentration: 0.0
 
 Ski_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad4_Ski_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smurf1_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad7_Smurf1_n
Compartment: nucleus
Initial concentration: 0.0
 
 pSmad3_Smad4_Ski_n
Compartment: nucleus
Initial concentration: 0.0
 
 Smad4_Smad3_n
Compartment: nucleus
Initial concentration: 0.0
 
 freePromoters
Compartment: nucleus
Initial concentration: 0.0999999951844375
 
 inactivePromoters
Compartment: nucleus
Initial concentration: 0.0
 
 geneProduct
Compartment: nucleus
Initial concentration: 0.0
 
 Arkadia_n
Compartment: nucleus
Initial concentration: 0.0
 
Global Parameters (10)
 
 TGFbeta
Value: 0.01
Constant
 
   allSnoN  
 
   allSmad7  
 
   allSmurf2  
 
   allSmad2  
 
   allSmad4  
 
   allPSmad3  
 
   allSmad3  
 
   allSmad4cyt  
 
   allSmad4nuc  
 
Smad_dissoc3 (1)
 
 k1
Value: 0.0492
Constant
 
Smad2_dephosphNuc (2)
 
 Km
Value: 40.0
Constant
 
 V
Value: 2.34
Constant
 
Smad_inhibComp2SnoN (2)
 
 k1
Value: 1.6
Constant
 
 k2
Value: 1.6
Constant
 
SnoN_degrad2 (1)
 
 k1
Value: 0.232
Constant
 
Smad_compNuc2 (1)
 
 k1
Value: 255.068
Constant
 
Smad2_dephosphNuc2 (2)
 
 Km
Value: 0.53
Constant
 
 V
Value: 3.51
Constant
 
Smad2_degrad (1)
 
 k1
Value: 0.2
Constant
 
Smad7-Smurf2 (2)
 
 k1
Value: 2.9
Constant
 
 k2
Value: 0.2
Constant
 
Rec_comp1 (1)
 
 k
Value: 9.45
Constant
 
Rec_comp2 (2)
 
 k1
Value: 0.03333
Constant
 
 k2
Value: 0.03333
Constant
 
SARA-comp2 (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.1
Constant
 
Smad2_phosph (2)
 
 k
Value: 1000.0
Constant
 
 km
Value: 0.0318
Constant
 
Smad2_phosphSARA (2)
 
 k
Value: 3.51
Constant
 
 km
Value: 0.53
Constant
 
Smad2-P_transp (1)
 
 k1
Value: 16.6
Constant
 
Smad_compCyt2 (1)
 
 k1
Value: 1000.0
Constant
 
Smad4_transp (2)
 
 k1
Value: 0.156
Constant
 
 k2
Value: 0.156
Constant
 
Smad_compTransp2 (1)
 
 k1
Value: 0.16
Constant
 
Smad7_transp (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.01
Constant
 
Smad7-Smurf2_transp (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.01
Constant
 
Rec_degrad1 (1)
 
 k1
Value: 1900.0
Constant
 
Rec_inhib (2)
 
 k1
Value: 8.69
Constant
 
 k2
Value: 0.01
Constant
 
fluxRecII (1)
 
 v
Value: 0.00146
Constant
 
fluxSara (2)
 
 k
Value: 1.0E-4
Constant
 
 k1
Value: 0.031
Constant
 
fluxSmad7 (2)
 
 k
Value: 1.0E-4
Constant
 
 k1
Value: 0.1
Constant
 
fluxSmurf2 (2)
 
 k
Value: 2.28E-4
Constant
 
 k1
Value: 0.0285
Constant
 
fluxSnoN (2)
 
 k
Value: 2.0E-5
Constant
 
 k1
Value: 5.5E-4
Constant
 
fluxRecI (1)
 
 v
Value: 0.0125
Constant
 
Smad4-SnoN (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.05288
Constant
 
Smad2_transp (2)
 
 k1
Value: 0.156
Constant
 
 k2
Value: 0.336
Constant
 
Rec_degrad (1)
 
 k1
Value: 0.027778
Constant
 
RecI_degrad (1)
 
 k1
Value: 0.027778
Constant
 
RecII_degrad (1)
 
 k1
Value: 0.027778
Constant
 
Rec_recycl (1)
 
 k1
Value: 0.03333
Constant
 
fluxSmad2 (1)
 
 v
Value: 0.0156
Constant
 
fluxSmad4 (1)
 
 v
Value: 0.01183
Constant
 
Smad4_degrad (1)
 
 k1
Value: 0.1266
Constant
 
SARA_degrad (1)
 
 k1
Value: 0.065
Constant
 
Smad2_dephospCyt (2)
 
 Km
Value: 3.51
Constant
 
 V
Value: 0.53
Constant
 
SnoN_degrad (1)
 
 k1
Value: 0.232
Constant
 
Smurf2_transp (2)
 
 k1
Value: 0.2333
Constant
 
 k2
Value: 1.8056
Constant
 
Smad2_cyt_degrad (1)
 
 k1
Value: 0.2
Constant
 
SnoN_trans (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.2
Constant
 
fluxSmad3 (1)
 
 v
Value: 0.04528
Constant
 
Smad3_cyt_degrad (1)
 
 k1
Value: 0.2
Constant
 
Smad3_dephospCyt (2)
 
 Km
Value: 3.51
Constant
 
 V
Value: 0.53
Constant
 
Smad3_dephospNuc (2)
 
 Km
Value: 40.0
Constant
 
 V
Value: 2.34
Constant
 
Smad3_dephospNuc2 (2)
 
 Km
Value: 0.53
Constant
 
 V
Value: 3.51
Constant
 
Smad3_phosph (2)
 
 k
Value: 1000.0
Constant
 
 km
Value: 0.0318
Constant
 
Smad3_phosphSARA (2)
 
 k
Value: 3.51
Constant
 
 km
Value: 0.53
Constant
 
Smad3_degrad (1)
 
 k1
Value: 0.2
Constant
 
Smad3_transp (2)
 
 k1
Value: 0.156
Constant
 
 k2
Value: 0.336
Constant
 
SARA-comp3 (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.1
Constant
 
Smad_dissoc2 (1)
 
 k1
Value: 0.0492
Constant
 
Smad3-P-transp (1)
 
 k1
Value: 16.6
Constant
 
Smad_compCyt3 (1)
 
 k1
Value: 1000.0
Constant
 
Smad_compNuc3 (1)
 
 k1
Value: 255.068
Constant
 
Smad_inhibComp3SnoN (2)
 
 k1
Value: 1.6
Constant
 
 k2
Value: 1.6
Constant
 
Smad_compTransp3 (1)
 
 k1
Value: 0.16
Constant
 
SnoN_degrad3 (1)
 
 k1
Value: 0.232
Constant
 
Smad7_degrad (1)
 
 k1
Value: 0.1
Constant
 
Ski_degrad (1)
 
 k1
Value: 0.232
Constant
 
Ski_trans (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.2
Constant
 
fluxSki (2)
 
 k
Value: 2.0E-5
Constant
 
 k1
Value: 5.5E-4
Constant
 
Smurf2_degrad (1)
 
 k1
Value: 0.05
Constant
 
Smad4-Ski (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.05288
Constant
 
Smad3-Ski_cyt (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.1
Constant
 
Smad7-Smurf1 (2)
 
 k1
Value: 2.9
Constant
 
 k2
Value: 0.2
Constant
 
fluxSmurf1 (2)
 
 k
Value: 1.0E-4
Constant
 
 k1
Value: 0.0022
Constant
 
Smad_inhibComp3Ski (2)
 
 k1
Value: 1.6
Constant
 
 k2
Value: 1.6
Constant
 
Rec_degrad2 (1)
 
 k1
Value: 1900.0
Constant
 
Smad7-Smurf1_transp (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 0.01
Constant
 
Smurf1_degrad (1)
 
 k1
Value: 0.5
Constant
 
Smurf1_transp (2)
 
 k1
Value: 0.05
Constant
 
 k2
Value: 3.0
Constant
 
Smad3-freePromot (2)
 
 k1
Value: 0.463
Constant
 
 k2
Value: 0.102
Constant
 
Smad2-freePromot (2)
 
 k1
Value: 0.463
Constant
 
 k2
Value: 0.102
Constant
 
Smad3-SnoN-freePromot (2)
 
 k1
Value: 0.2
Constant
 
 k2
Value: 0.2
Constant
 
Smad2-SnoN-gene (2)
 
 k1
Value: 0.2
Constant
 
 k2
Value: 0.2
Constant
 
Smad3-Ski-freePromot (2)
 
 k1
Value: 0.2
Constant
 
 k2
Value: 0.2
Constant
 
Smad_inhibComp2Ski (2)
 
 k1
Value: 1.6
Constant
 
 k2
Value: 1.6
Constant
 
Smad2-Ski-gene (2)
 
 k1
Value: 0.2
Constant
 
 k2
Value: 0.2
Constant
 
Smad4-freePromot (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.1
Constant
 
Smad2-Ski_cyt (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.1
Constant
 
Smad2-Snon (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 1.0
Constant
 
Smad3-Snon (2)
 
 k1
Value: 1.0
Constant
 
 k2
Value: 1.0
Constant
 
Smad2-comp-degrad (1)
 
 k1
Value: 0.0050
Constant
 
Samd3-comp-degrad (1)
 
 k1
Value: 0.0050
Constant
 
fluxArkadia (1)
 
 v
Value: 2.0E-5
Constant
 
Arkadia_deg (1)
 
 k1
Value: 0.1
Constant
 
SnoN-deg2 (1)
 
 k1
Value: 0.1
Constant
 
SnoN-deg3 (1)
 
 k1
Value: 0.1
Constant
 
transArkadia (2)
 
 k1
Value: 0.1
Constant
 
 k2
Value: 0.1
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000410

Curator's comment: (updated: 10 Feb 2012 11:44:09 GMT)

Figure 2 of the reference publication has been reproduced here. The data were obtained by simulating the model using SBMLodeSolver and plotted using Gnuplot.

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