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BIOMD0000000640 - DallePezze2016 - Activation of AMPK and mTOR by amino acids

 

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Reference Publication
Publication ID: 27869123
Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn U, Horvatovich P, Shanley DP, Thedieck K.
A systems study reveals concurrent activation of AMPK and mTOR by amino acids.
Nat Commun 2016 Nov; 7: 13254
Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.  [more]
Model
Original Model: http://www.nature.com/arti...
Submitter: Piero Dalle Pezze
Submission ID: MODEL1702270000
Submission Date: 27 Feb 2017 14:13:02 UTC
Last Modification Date: 22 May 2017 08:24:09 UTC
Creation Date: 07 May 2015 16:00:48 UTC
Encoders:  
   
set #1
bqbiol:hasProperty Gene Ontology regulation of autophagy
Mathematical Modelling Ontology ordinary differential equation model
set #2
bqbiol:hasTaxon Taxonomy Mammalia
Notes
DallePezze2016 - Activation of AMPK and mTOR by amino acids (Model 3)
This model is as described in the Supplementary Software 3 of the reference publication: SBML model similar to Model S2, but including a more complex p70-S6K module.

This model is described in the article:

Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn U, Horvatovich P, Shanley DP, Thedieck K.
Nat Commun 2016 Nov; 7: 13254

Abstract:

Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase ? (CaMKK?). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes.

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.

Model
Publication ID: 27869123 Submission Date: 27 Feb 2017 14:13:02 UTC Last Modification Date: 22 May 2017 08:24:09 UTC Creation Date: 07 May 2015 16:00:48 UTC
Mathematical expressions
Reactions
reaction_1 reaction_2 reaction_3 reaction_4
reaction_5 reaction_6 reaction_7 reaction_8
reaction_9 reaction_10 reaction_11 reaction_12
reaction_13 reaction_14 reaction_15 reaction_16
reaction_17 reaction_18 reaction_19 reaction_20
reaction_21 reaction_22 reaction_23 reaction_24
reaction_25 reaction_26 reaction_27 reaction_28
reaction_29 reaction_30 reaction_31 reaction_32
reaction_33 reaction_34 reaction_35 reaction_36
reaction_37 reaction_38 reaction_39 reaction_40
reaction_41 reaction_42 reaction_43 reaction_44
reaction_45 reaction_46 reaction_47 reaction_48
Rules
Assignment Rule (variable: Insulin) Assignment Rule (variable: Amino_Acids) Assignment Rule (variable: IR_beta_pY1146_obs) Assignment Rule (variable: IRS_pS636_obs)
Assignment Rule (variable: AMPK_pT172_obs) Assignment Rule (variable: Akt_pT308_obs) Assignment Rule (variable: Akt_pS473_obs) Assignment Rule (variable: TSC1_TSC2_pS1387_obs)
Assignment Rule (variable: mTOR_pS2448_obs) Assignment Rule (variable: mTOR_pS2481_obs) Assignment Rule (variable: p70_S6K_pT229_obs) Assignment Rule (variable: p70_S6K_pT389_obs)
Assignment Rule (variable: PRAS40_pT246_obs) Assignment Rule (variable: PRAS40_pS183_obs)    
Physical entities
Compartments Species
Cell IR_beta IR_beta_pY1146 IR_beta_refractory
IRS IRS_p IRS_pS636
AMPK AMPK_pT172 Akt
Akt_pT308 Akt_pS473 Akt_pT308_pS473
TSC1_TSC2 TSC1_TSC2_pT1462 TSC1_TSC2_pS1387
mTORC1 mTORC1_pS2448 mTORC2
mTORC2_pS2481 p70_S6K p70_S6K_pT229
p70_S6K_pT389 p70_S6K_pT229_pT389 PRAS40
PRAS40_pT246 PRAS40_pS183 PRAS40_pT246_pS183
PI3K_variant PI3K_variant_p PI3K_PDK1
PI3K_p_PDK1 Insulin Amino_Acids
IR_beta_pY1146_obs IRS_pS636_obs AMPK_pT172_obs
Akt_pT308_obs Akt_pS473_obs TSC1_TSC2_pS1387_obs
mTOR_pS2448_obs mTOR_pS2481_obs p70_S6K_pT229_obs
p70_S6K_pT389_obs PRAS40_pT246_obs PRAS40_pS183_obs
Global parameters
IRS_phos_by_Amino_Acids AMPK_T172_phos_by_Amino_Acids mTORC2_S2481_phos_by_Amino_Acids IR_beta_phos_by_Insulin
IR_beta_pY1146_dephos IR_beta_ready IRS_phos_by_IR_beta_pY1146 IRS_p_phos_by_p70_S6K_pT229_pT389
IRS_phos_by_p70_S6K_pT229_pT389 IRS_pS636_turnover AMPK_T172_phos AMPK_pT172_dephos
Akt_S473_phos_by_mTORC2_pS2481_first Akt_S473_phos_by_mTORC2_pS2481_second Akt_T308_phos_by_PI3K_p_PDK1_first Akt_T308_phos_by_PI3K_p_PDK1_second
Akt_pT308_dephos_first Akt_pT308_dephos_second Akt_pS473_dephos_first Akt_pS473_dephos_second
TSC1_TSC2_S1387_phos_by_AMPK_pT172 TSC1_TSC2_T1462_phos_by_Akt_pT308 TSC1_TSC2_pS1387_dephos TSC1_TSC2_pT1462_dephos
mTORC1_pS2448_dephos_by_TSC1_TSC2 mTORC1_S2448_activation_by_Amino_Acids mTORC2_pS2481_dephos mTORC2_S2481_phos_by_PI3K_variant_p
p70_S6K_T229_phos_by_PI3K_p_PDK1_first p70_S6K_T229_phos_by_PI3K_p_PDK1_second p70_S6K_T389_phos_by_mTORC1_pS2448_first p70_S6K_T389_phos_by_mTORC1_pS2448_second
p70_S6K_pT229_dephos_first p70_S6K_pT229_dephos_second p70_S6K_pT389_dephos_first p70_S6K_pT389_dephos_second
PRAS40_S183_phos_by_mTORC1_pS2448_first PRAS40_S183_phos_by_mTORC1_pS2448_second PRAS40_T246_phos_by_Akt_pT308_first PRAS40_T246_phos_by_Akt_pT308_second
PRAS40_pS183_dephos_first PRAS40_pS183_dephos_second PRAS40_pT246_dephos_first PRAS40_pT246_dephos_second
PI3K_p_PDK1_dephos PI3K_PDK1_phos_by_IRS_p PI3K_variant_p_dephos PI3K_variant_phos_by_IR_beta_pY1146
scale_IR_beta_pY1146_obs scale_IRS_pS636_obs scale_AMPK_pT172_obs scale_Akt_pT308_obs
scale_Akt_pS473_obs scale_TSC1_TSC2_pS1387_obs scale_mTOR_pS2448_obs scale_mTOR_pS2481_obs
scale_p70_S6K_pT229_obs scale_p70_S6K_pT389_obs scale_PRAS40_pT246_obs scale_PRAS40_pS183_obs
Reactions (48)
 
 reaction_1 [IRS] → [IRS_p];   {Amino_Acids}
 
 reaction_2 [AMPK] → [AMPK_pT172];   {Amino_Acids}
 
 reaction_3 [mTORC2] → [mTORC2_pS2481];   {Amino_Acids}
 
 reaction_4 [IR_beta] → [IR_beta_pY1146];   {Insulin}
 
 reaction_5 [IR_beta_pY1146] → [IR_beta_refractory];  
 
 reaction_6 [IR_beta_refractory] → [IR_beta];  
 
 reaction_7 [IRS] → [IRS_p];   {IR_beta_pY1146}
 
 reaction_8 [IRS_p] → [IRS_pS636];   {p70_S6K_pT229_pT389}
 
 reaction_9 [IRS] → [IRS_pS636];   {p70_S6K_pT229_pT389}
 
 reaction_10 [IRS_pS636] → [IRS];  
 
 reaction_11 [PI3K_p_PDK1] → [PI3K_PDK1];  
 
 reaction_12 [PI3K_PDK1] → [PI3K_p_PDK1];   {IRS_p}
 
 reaction_13 [PI3K_variant_p] → [PI3K_variant];  
 
 reaction_14 [PI3K_variant] → [PI3K_variant_p];   {IR_beta_pY1146}
 
 reaction_15 [AMPK] → [AMPK_pT172];   {IRS_p}
 
 reaction_16 [AMPK_pT172] → [AMPK];  
 
 reaction_17 [Akt] → [Akt_pT308];   {PI3K_p_PDK1}
 
 reaction_18 [Akt] → [Akt_pS473];   {mTORC2_pS2481}
 
 reaction_19 [Akt_pS473] → [Akt_pT308_pS473];   {PI3K_p_PDK1}
 
 reaction_20 [Akt_pT308] → [Akt_pT308_pS473];   {mTORC2_pS2481}
 
 reaction_21 [Akt_pT308] → [Akt];  
 
 reaction_22 [Akt_pS473] → [Akt];  
 
 reaction_23 [Akt_pT308_pS473] → [Akt_pS473];  
 
 reaction_24 [Akt_pT308_pS473] → [Akt_pT308];  
 
 reaction_25 [TSC1_TSC2] → [TSC1_TSC2_pS1387];   {AMPK_pT172}
 
 reaction_26 [TSC1_TSC2] → [TSC1_TSC2_pT1462];   {Akt_pT308} , {Akt_pT308_pS473}
 
 reaction_27 [TSC1_TSC2_pS1387] → [TSC1_TSC2];  
 
 reaction_28 [TSC1_TSC2_pT1462] → [TSC1_TSC2];  
 
 reaction_29 [mTORC1_pS2448] → [mTORC1];   {TSC1_TSC2} , {TSC1_TSC2_pS1387}
 
 reaction_30 [mTORC1] → [mTORC1_pS2448];   {Amino_Acids}
 
 reaction_31 [mTORC2] → [mTORC2_pS2481];   {PI3K_variant_p}
 
 reaction_32 [mTORC2_pS2481] → [mTORC2];  
 
 reaction_33 [p70_S6K] → [p70_S6K_pT229];   {PI3K_p_PDK1}
 
 reaction_34 [p70_S6K] → [p70_S6K_pT389];   {mTORC1_pS2448}
 
 reaction_35 [p70_S6K_pT389] → [p70_S6K_pT229_pT389];   {PI3K_p_PDK1}
 
 reaction_36 [p70_S6K_pT229] → [p70_S6K_pT229_pT389];   {mTORC1_pS2448}
 
 reaction_37 [p70_S6K_pT229] → [p70_S6K];  
 
 reaction_38 [p70_S6K_pT389] → [p70_S6K];  
 
 reaction_39 [p70_S6K_pT229_pT389] → [p70_S6K_pT389];  
 
 reaction_40 [p70_S6K_pT229_pT389] → [p70_S6K_pT229];  
 
 reaction_41 [PRAS40] → [PRAS40_pS183];   {mTORC1_pS2448}
 
 reaction_42 [PRAS40] → [PRAS40_pT246];   {Akt_pT308} , {Akt_pT308_pS473}
 
 reaction_43 [PRAS40_pS183] → [PRAS40_pT246_pS183];   {Akt_pT308} , {Akt_pT308_pS473}
 
 reaction_44 [PRAS40_pT246] → [PRAS40_pT246_pS183];   {mTORC1_pS2448}
 
 reaction_45 [PRAS40_pS183] → [PRAS40];  
 
 reaction_46 [PRAS40_pT246] → [PRAS40];  
 
 reaction_47 [PRAS40_pT246_pS183] → [PRAS40_pT246];  
 
 reaction_48 [PRAS40_pT246_pS183] → [PRAS40_pS183];  
 
Rules (14)
 
 Assignment Rule (name: Insulin) Insulin = piecewise(0, time < 0, 0)
 
 Assignment Rule (name: Amino_Acids) Amino_Acids = piecewise(0, time < 0, 1)
 
 Assignment Rule (name: IR_beta_pY1146_obs) IR_beta_pY1146_obs = IR_beta_pY1146
 
 Assignment Rule (name: IRS_pS636_obs) IRS_pS636_obs = IRS_pS636
 
 Assignment Rule (name: AMPK_pT172_obs) AMPK_pT172_obs = AMPK_pT172
 
 Assignment Rule (name: Akt_pT308_obs) Akt_pT308_obs = Akt_pT308+Akt_pT308_pS473
 
 Assignment Rule (name: Akt_pS473_obs) Akt_pS473_obs = Akt_pS473+Akt_pT308_pS473
 
 Assignment Rule (name: TSC1_TSC2_pS1387_obs) TSC1_TSC2_pS1387_obs = TSC1_TSC2_pS1387
 
 Assignment Rule (name: mTOR_pS2448_obs) mTOR_pS2448_obs = mTORC1_pS2448
 
 Assignment Rule (name: mTOR_pS2481_obs) mTOR_pS2481_obs = mTORC2_pS2481
 
 Assignment Rule (name: p70_S6K_pT229_obs) p70_S6K_pT229_obs = p70_S6K_pT229+p70_S6K_pT229_pT389
 
 Assignment Rule (name: p70_S6K_pT389_obs) p70_S6K_pT389_obs = p70_S6K_pT389+p70_S6K_pT229_pT389
 
 Assignment Rule (name: PRAS40_pT246_obs) PRAS40_pT246_obs = PRAS40_pT246+PRAS40_pT246_pS183
 
 Assignment Rule (name: PRAS40_pS183_obs) PRAS40_pS183_obs = PRAS40_pS183+PRAS40_pT246_pS183
 
Functions (27)
 
 Function for reaction_8 lambda(IRS_p, IRS_p_phos_by_p70_S6K_pT229_pT389, p70_S6K_pT229_pT389, IRS_p_phos_by_p70_S6K_pT229_pT389*IRS_p*p70_S6K_pT229_pT389)
 
 Function for reaction_3 lambda(Amino_Acids, mTORC2, mTORC2_S2481_phos_by_Amino_Acids, mTORC2_S2481_phos_by_Amino_Acids*mTORC2*Amino_Acids)
 
 Function for reaction_20 lambda(Akt_S473_phos_by_mTORC2_pS2481_second, Akt_pT308, mTORC2_pS2481, Akt_S473_phos_by_mTORC2_pS2481_second*Akt_pT308*mTORC2_pS2481)
 
 Function for reaction_29 lambda(TSC1_TSC2, TSC1_TSC2_pS1387, mTORC1_pS2448, mTORC1_pS2448_dephos_by_TSC1_TSC2, mTORC1_pS2448_dephos_by_TSC1_TSC2*mTORC1_pS2448*(TSC1_TSC2+TSC1_TSC2_pS1387))
 
 Function for reaction_33 lambda(PI3K_p_PDK1, p70_S6K, p70_S6K_T229_phos_by_PI3K_p_PDK1_first, p70_S6K_T229_phos_by_PI3K_p_PDK1_first*p70_S6K*PI3K_p_PDK1)
 
 Function for reaction_31 lambda(PI3K_variant_p, mTORC2, mTORC2_S2481_phos_by_PI3K_variant_p, mTORC2_S2481_phos_by_PI3K_variant_p*mTORC2*PI3K_variant_p)
 
 Function for reaction_2 lambda(AMPK, AMPK_T172_phos_by_Amino_Acids, Amino_Acids, AMPK_T172_phos_by_Amino_Acids*AMPK*Amino_Acids)
 
 Function for reaction_4 lambda(IR_beta, IR_beta_phos_by_Insulin, Insulin, IR_beta_phos_by_Insulin*IR_beta*Insulin)
 
 Function for reaction_36 lambda(mTORC1_pS2448, p70_S6K_T389_phos_by_mTORC1_pS2448_second, p70_S6K_pT229, p70_S6K_T389_phos_by_mTORC1_pS2448_second*p70_S6K_pT229*mTORC1_pS2448)
 
 Function for reaction_35 lambda(PI3K_p_PDK1, p70_S6K_T229_phos_by_PI3K_p_PDK1_second, p70_S6K_pT389, p70_S6K_T229_phos_by_PI3K_p_PDK1_second*p70_S6K_pT389*PI3K_p_PDK1)
 
 Function for reaction_26 lambda(Akt_pT308, Akt_pT308_pS473, TSC1_TSC2, TSC1_TSC2_T1462_phos_by_Akt_pT308, TSC1_TSC2_T1462_phos_by_Akt_pT308*TSC1_TSC2*(Akt_pT308+Akt_pT308_pS473))
 
 Function for reaction_17 lambda(Akt, Akt_T308_phos_by_PI3K_p_PDK1_first, PI3K_p_PDK1, Akt_T308_phos_by_PI3K_p_PDK1_first*Akt*PI3K_p_PDK1)
 
 Function for reaction_44 lambda(PRAS40_S183_phos_by_mTORC1_pS2448_second, PRAS40_pT246, mTORC1_pS2448, PRAS40_S183_phos_by_mTORC1_pS2448_second*PRAS40_pT246*mTORC1_pS2448)
 
 Function for reaction_43 lambda(Akt_pT308, Akt_pT308_pS473, PRAS40_T246_phos_by_Akt_pT308_second, PRAS40_pS183, PRAS40_T246_phos_by_Akt_pT308_second*PRAS40_pS183*(Akt_pT308+Akt_pT308_pS473))
 
 Function for reaction_9 lambda(IRS, IRS_phos_by_p70_S6K_pT229_pT389, p70_S6K_pT229_pT389, IRS_phos_by_p70_S6K_pT229_pT389*IRS*p70_S6K_pT229_pT389)
 
 Function for reaction_25 lambda(AMPK_pT172, TSC1_TSC2, TSC1_TSC2_S1387_phos_by_AMPK_pT172, TSC1_TSC2_S1387_phos_by_AMPK_pT172*TSC1_TSC2*AMPK_pT172)
 
 Function for reaction_14 lambda(IR_beta_pY1146, PI3K_variant, PI3K_variant_phos_by_IR_beta_pY1146, PI3K_variant_phos_by_IR_beta_pY1146*PI3K_variant*IR_beta_pY1146)
 
 Function for reaction_18 lambda(Akt, Akt_S473_phos_by_mTORC2_pS2481_first, mTORC2_pS2481, Akt_S473_phos_by_mTORC2_pS2481_first*Akt*mTORC2_pS2481)
 
 Function for reaction_30 lambda(Amino_Acids, mTORC1, mTORC1_S2448_activation_by_Amino_Acids, mTORC1_S2448_activation_by_Amino_Acids*mTORC1*Amino_Acids)
 
 Function for reaction_15 lambda(AMPK, AMPK_T172_phos, IRS_p, AMPK_T172_phos*AMPK*IRS_p)
 
 Function for reaction_19 lambda(Akt_T308_phos_by_PI3K_p_PDK1_second, Akt_pS473, PI3K_p_PDK1, Akt_T308_phos_by_PI3K_p_PDK1_second*Akt_pS473*PI3K_p_PDK1)
 
 Function for reaction_12 lambda(IRS_p, PI3K_PDK1, PI3K_PDK1_phos_by_IRS_p, PI3K_PDK1_phos_by_IRS_p*PI3K_PDK1*IRS_p)
 
 Function for reaction_34 lambda(mTORC1_pS2448, p70_S6K, p70_S6K_T389_phos_by_mTORC1_pS2448_first, p70_S6K_T389_phos_by_mTORC1_pS2448_first*p70_S6K*mTORC1_pS2448)
 
 Function for reaction_7 lambda(IRS, IRS_phos_by_IR_beta_pY1146, IR_beta_pY1146, IRS_phos_by_IR_beta_pY1146*IRS*IR_beta_pY1146)
 
 Function for reaction_41 lambda(PRAS40, PRAS40_S183_phos_by_mTORC1_pS2448_first, mTORC1_pS2448, PRAS40_S183_phos_by_mTORC1_pS2448_first*PRAS40*mTORC1_pS2448)
 
 Function for reaction_42 lambda(Akt_pT308, Akt_pT308_pS473, PRAS40, PRAS40_T246_phos_by_Akt_pT308_first, PRAS40_T246_phos_by_Akt_pT308_first*PRAS40*(Akt_pT308+Akt_pT308_pS473))
 
 Function for reaction_1 lambda(Amino_Acids, IRS, IRS_phos_by_Amino_Acids, IRS_phos_by_Amino_Acids*IRS*Amino_Acids)
 
 Cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 IR_beta
Compartment: Cell
Initial concentration: 50.0
 
   IR_beta_pY1146
Compartment: Cell
Initial concentration: 0.0
 
   IR_beta_refractory
Compartment: Cell
Initial concentration: 0.0
 
 IRS
Compartment: Cell
Initial concentration: 150.0
 
   IRS_p
Compartment: Cell
Initial concentration: 0.0
 
   IRS_pS636
Compartment: Cell
Initial concentration: 0.0
 
 AMPK
Compartment: Cell
Initial concentration: 50.0
 
   AMPK_pT172
Compartment: Cell
Initial concentration: 0.0
 
   Akt
Compartment: Cell
Initial concentration: 300.0
 
   Akt_pT308
Compartment: Cell
Initial concentration: 0.0
 
   Akt_pS473
Compartment: Cell
Initial concentration: 0.0
 
   Akt_pT308_pS473
Compartment: Cell
Initial concentration: 0.0
 
   TSC1_TSC2
Compartment: Cell
Initial concentration: 50.0
 
   TSC1_TSC2_pT1462
Compartment: Cell
Initial concentration: 0.0
 
   TSC1_TSC2_pS1387
Compartment: Cell
Initial concentration: 0.0
 
   mTORC1
Compartment: Cell
Initial concentration: 100.0
 
   mTORC1_pS2448
Compartment: Cell
Initial concentration: 0.0
 
   mTORC2
Compartment: Cell
Initial concentration: 100.0
 
   mTORC2_pS2481
Compartment: Cell
Initial concentration: 0.0
 
   p70_S6K
Compartment: Cell
Initial concentration: 300.0
 
   p70_S6K_pT229
Compartment: Cell
Initial concentration: 0.0
 
   p70_S6K_pT389
Compartment: Cell
Initial concentration: 0.0
 
   p70_S6K_pT229_pT389
Compartment: Cell
Initial concentration: 0.0
 
   PRAS40
Compartment: Cell
Initial concentration: 20.0
 
   PRAS40_pT246
Compartment: Cell
Initial concentration: 0.0
 
   PRAS40_pS183
Compartment: Cell
Initial concentration: 0.0
 
   PRAS40_pT246_pS183
Compartment: Cell
Initial concentration: 0.0
 
 PI3K_variant
Compartment: Cell
Initial concentration: 50.0
 
   PI3K_variant_p
Compartment: Cell
Initial concentration: 0.0
 
 PI3K_PDK1
Compartment: Cell
Initial concentration: 50.0
 
 PI3K_p_PDK1
Compartment: Cell
Initial concentration: 0.0
 
  Insulin
Compartment: Cell
Initial concentration: 0.0
 
  Amino_Acids
Compartment: Cell
Initial concentration: 1.0
 
   IR_beta_pY1146_obs
Compartment: Cell
Initial concentration: 0.0
 
   IRS_pS636_obs
Compartment: Cell
Initial concentration: 0.0
 
   AMPK_pT172_obs
Compartment: Cell
Initial concentration: 0.0
 
   Akt_pT308_obs
Compartment: Cell
Initial concentration: 0.0
 
   Akt_pS473_obs
Compartment: Cell
Initial concentration: 0.0
 
   TSC1_TSC2_pS1387_obs
Compartment: Cell
Initial concentration: 0.0
 
   mTOR_pS2448_obs
Compartment: Cell
Initial concentration: 0.0
 
   mTOR_pS2481_obs
Compartment: Cell
Initial concentration: 0.0
 
   p70_S6K_pT229_obs
Compartment: Cell
Initial concentration: 0.0
 
   p70_S6K_pT389_obs
Compartment: Cell
Initial concentration: 0.0
 
   PRAS40_pT246_obs
Compartment: Cell
Initial concentration: 0.0
 
   PRAS40_pS183_obs
Compartment: Cell
Initial concentration: 0.0
 
Global Parameters (60)
 
   IRS_phos_by_Amino_Acids
Value: 0.0331672
Constant
 
   AMPK_T172_phos_by_Amino_Acids
Value: 17.6284
Constant
 
   mTORC2_S2481_phos_by_Amino_Acids
Value: 0.0268658
Constant
 
   IR_beta_phos_by_Insulin
Value: 0.0203796
Constant
 
   IR_beta_pY1146_dephos
Value: 0.493514
Constant
 
   IR_beta_ready
Value: 323.611
Constant
 
   IRS_phos_by_IR_beta_pY1146
Value: 2.11894
Constant
 
   IRS_p_phos_by_p70_S6K_pT229_pT389
Value: 0.338859859949792
Constant
 
   IRS_phos_by_p70_S6K_pT229_pT389
Value: 0.0863775267376444
Constant
 
   IRS_pS636_turnover
Value: 25.0
Constant
 
   AMPK_T172_phos
Value: 0.490602
Constant
 
   AMPK_pT172_dephos
Value: 165.704
Constant
 
   Akt_S473_phos_by_mTORC2_pS2481_first
Value: 1.31992E-5
Constant
 
   Akt_S473_phos_by_mTORC2_pS2481_second
Value: 0.159093
Constant
 
   Akt_T308_phos_by_PI3K_p_PDK1_first
Value: 7.47437
Constant
 
   Akt_T308_phos_by_PI3K_p_PDK1_second
Value: 7.47345
Constant
 
   Akt_pT308_dephos_first
Value: 88.9654
Constant
 
   Akt_pT308_dephos_second
Value: 88.9639
Constant
 
   Akt_pS473_dephos_first
Value: 0.376999
Constant
 
   Akt_pS473_dephos_second
Value: 0.380005
Constant
 
   TSC1_TSC2_S1387_phos_by_AMPK_pT172
Value: 0.00175772
Constant
 
   TSC1_TSC2_T1462_phos_by_Akt_pT308
Value: 1.52417
Constant
 
 TSC1_TSC2_pS1387_dephos
Value: 0.25319
Constant
 
 TSC1_TSC2_pT1462_dephos
Value: 147.239
Constant
 
   mTORC1_pS2448_dephos_by_TSC1_TSC2
Value: 0.00869774
Constant
 
   mTORC1_S2448_activation_by_Amino_Acids
Value: 0.0156992
Constant
 
   mTORC2_pS2481_dephos
Value: 1.42511
Constant
 
   mTORC2_S2481_phos_by_PI3K_variant_p
Value: 0.120736
Constant
 
   p70_S6K_T229_phos_by_PI3K_p_PDK1_first
Value: 0.0133520172873009
Constant
 
   p70_S6K_T229_phos_by_PI3K_p_PDK1_second
Value: 1.00000002814509E-6
Constant
 
   p70_S6K_T389_phos_by_mTORC1_pS2448_first
Value: 0.00261303413778722
Constant
 
   p70_S6K_T389_phos_by_mTORC1_pS2448_second
Value: 0.110720890919343
Constant
 
   p70_S6K_pT229_dephos_first
Value: 1.00000012897033E-6
Constant
 
   p70_S6K_pT229_dephos_second
Value: 0.159201353240651
Constant
 
   p70_S6K_pT389_dephos_first
Value: 1.10036057608758
Constant
 
   p70_S6K_pT389_dephos_second
Value: 1.10215267954479
Constant
 
   PRAS40_S183_phos_by_mTORC1_pS2448_first
Value: 0.15881
Constant
 
   PRAS40_S183_phos_by_mTORC1_pS2448_second
Value: 0.0683009
Constant
 
   PRAS40_T246_phos_by_Akt_pT308_first
Value: 0.279344
Constant
 
   PRAS40_T246_phos_by_Akt_pT308_second
Value: 0.279401
Constant
 
   PRAS40_pS183_dephos_first
Value: 1.8706
Constant
 
   PRAS40_pS183_dephos_second
Value: 1.88453
Constant
 
   PRAS40_pT246_dephos_first
Value: 11.8759
Constant
 
   PRAS40_pT246_dephos_second
Value: 11.876
Constant
 
   PI3K_p_PDK1_dephos
Value: 0.18913343080532
Constant
 
   PI3K_PDK1_phos_by_IRS_p
Value: 1.87226757782201E-4
Constant
 
   PI3K_variant_p_dephos
Value: 0.108074886441184
Constant
 
   PI3K_variant_phos_by_IR_beta_pY1146
Value: 5.49027801822575E-4
Constant
 
 scale_IR_beta_pY1146_obs
Value: 1.0
Constant
 
   scale_IRS_pS636_obs
Value: 1.0
Constant
 
 scale_AMPK_pT172_obs
Value: 1.0
Constant
 
 scale_Akt_pT308_obs
Value: 1.0
Constant
 
 scale_Akt_pS473_obs
Value: 1.0
Constant
 
 scale_TSC1_TSC2_pS1387_obs
Value: 1.0
Constant
 
 scale_mTOR_pS2448_obs
Value: 1.0
Constant
 
 scale_mTOR_pS2481_obs
Value: 1.0
Constant
 
 scale_p70_S6K_pT229_obs
Value: 1.0
Constant
 
 scale_p70_S6K_pT389_obs
Value: 1.0
Constant
 
 scale_PRAS40_pT246_obs
Value: 1.0
Constant
 
 scale_PRAS40_pS183_obs
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000640

Curator's comment: (updated: 19 May 2017 17:35:01 GMT)

We reproduce panels (from figure 2C) showing time series plots for Insulin, AMPK pT172 and Art pT308.

The simulations were carried out using SBMLsimulator (version 1.2.1) and the plots were generated using Matlab.

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