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BIOMD0000000594 - Capuani2015 - Binding of Cbl and Gbr2 to EGFR (Multisite Phosphorylation Model - MPM)

  
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Reference Publication
Publication ID: 26264748
Capuani F, Conte A, Argenzio E, Marchetti L, Priami C, Polo S, Di Fiore PP, Sigismund S, Ciliberto A.
Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells.
Nat Commun 2015; 6: 7999
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, Milan 20139, Italy.  [more]
Model
Original Model: BIOMD0000000594.origin
Submitter: Fabrizio Capuani
Submission ID: MODEL1505190001
Submission Date: 19 May 2015 19:46:44 UTC
Last Modification Date: 19 Apr 2016 21:55:48 UTC
Creation Date: 10 Feb 2016 14:07:57 UTC
Encoders:  Fabrizio Capuani
   Alastair Hume
set #1
bqbiol:hasProperty Human Disease Ontology cancer
set #2
bqbiol:isVersionOf Gene Ontology epidermal growth factor receptor signaling pathway
set #3
bqbiol:occursIn Brenda Tissue Ontology HeLa cell
set #4
bqbiol:hasTaxon Taxonomy Homo sapiens
Notes
Model
Publication ID: 26264748 Submission Date: 19 May 2015 19:46:44 UTC Last Modification Date: 19 Apr 2016 21:55:48 UTC Creation Date: 10 Feb 2016 14:07:57 UTC
Mathematical expressions
Reactions
EGFR_10UU has site Y1045 dephosphorylated EGFR_01UU has site Y1068/Y1086 dephosphorylated EGFR_11UU has site Y1045 dephosphorylated EGFR_11UU has site Y1068/Y1086 dephosphorylated
EGFR_11CU has site Y1068/Y1086 dephosphorylated EGFR_11LU has site Y1068/Y1086 dephosphorylated EGFR_11UG has site Y1045 dephosphorylated EGFR_11UL has site Y1045 dephosphorylated
EGFR_02UU has site Y1068/Y1086 dephosphorylated EGFR_02UG has site Y1068/Y1-86 dephosphorylated EGFR_02UL has site Y1068/Y1-86 dephosphorylated EGFR_12UU has site Y1045 dephosphorylated
EGFR_12UU has site Y1068/Y1086 dephosphorylated EGFR_12CU has site Y1068/Y1086 dephosphorylated EGFR_12LU has site Y1068/Y1086 dephosphorylated EGFR_12UG has site Y1045 dephosphorylated
EGFR_12UG has site Y1068/Y1-86 dephosphorylated EGFR_12UL has site Y1045 dephosphorylated EGFR_12UL has site Y1068/Y1-86 dephosphorylated EGFR_12CG has site Y1068/Y1-86 dephosphorylated
EGFR_12CC has site Y1068/Y1-86 dephosphorylated EGFR_12LG has site Y1068/Y1-86 dephosphorylated EGFR_00UU has site Y1045 phosphorylated EGFR_00UU has site Y1068/Y1086 phosphorylated
EGFR_10UU has site Y1068/Y1086 phosphorylated EGFR_10CU has site Y1068/Y1086 phosphorylated EGFR_10LU has site Y1068/Y1086 phosphorylated EGFR_01UU has site Y1045 phosphorylated
EGFR_01UU has site Y1068/Y1086 phosphorylated EGFR_01UG has site Y1045 phosphorylated EGFR_01UG has site Y1068/Y1086 phosphorylated EGFR_01UL has site Y1045 phosphorylated
EGFR_01UL has site Y1068/Y1086 phosphorylated EGFR_11UU has site Y1068/Y1086 phosphorylated EGFR_11CU has site Y1068/Y1086 phosphorylated EGFR_11LU has site Y1068/Y1086 phosphorylated
EGFR_11UG has site Y1068/Y1086 phosphorylated EGFR_11UL has site Y1068/Y1086 phosphorylated EGFR_11CG has site Y1068/Y1086 phosphorylated EGFR_11CC has site Y1068/Y1086 phosphorylated
EGFR_11LG has site Y1068/Y1086 phosphorylated EGFR_02UU has site Y1045 phosphorylated EGFR_02UG has site Y1045 phosphorylated EGFR_02UL has site Y1045 phosphorylated
Cbl and Grb2 bind yielding CG CG dissociates to Cbl and Grb2 Cbl and EGFR_10UU bind yielding EGFR_10CU EGFR_10CU dissociates to Cbl and EGFR_10UU
CG and EGFR_10UU bind yielding EGFR_10LU EGFR_10LU dissociates to CG and EGFR_10UU Grb2 and EGFR_10CU bind yielding EGFR_10LU EGFR_10LU dissociates to Grb2 and EGFR_10CU
Grb2 and EGFR_01UU bind yielding EGFR_01UG EGFR_01UG dissociates to Grb2 and EGFR_01UU CG and EGFR_01UU bind yielding EGFR_01UL EGFR_01UL dissociates to CG and EGFR_01UU
Cbl and EGFR_01UG bind yielding EGFR_01UL EGFR_01UL dissociates to Cbl and EGFR_01UG Cbl and EGFR_11UU bind yielding EGFR_11CU EGFR_11CU dissociates to Cbl and EGFR_11UU
CG and EGFR_11UU bind yielding EGFR_11LU EGFR_11LU dissociates to CG and EGFR_11UU Grb2 and EGFR_11UU bind yielding EGFR_11UG EGFR_11UG dissociates to Grb2 and EGFR_11UU
CG and EGFR_11UU bind yielding EGFR_11UL EGFR_11UL dissociates to CG and EGFR_11UU Grb2 and EGFR_11CU bind yielding EGFR_11LU EGFR_11LU dissociates to Grb2 and EGFR_11CU
Grb2 and EGFR_11CU bind yielding EGFR_11CG EGFR_11CG dissociates to Grb2 and EGFR_11CU Grb2 and EGFR_11LU bind yielding EGFR_11LG EGFR_11LG dissociates to Grb2 and EGFR_11LU
EGFR_11LU transforms in (singly-bound -> doubly-bound) EGFR_11CC EGFR_11CC tranforms in (doubly-bound -> singly-bound) EGFR_11LU Cbl and EGFR_11UG bind yielding EGFR_11CG EGFR_11CG dissociates to Cbl and EGFR_11UG
CG and EGFR_11UG bind yielding EGFR_11LG EGFR_11LG dissociates to CG and EGFR_11UG Cbl and EGFR_11UG bind yielding EGFR_11UL EGFR_11UL dissociates to Cbl and EGFR_11UG
EGFR_11UL transforms in (singly-bound -> doubly-bound) EGFR_11CC EGFR_11CC tranforms in (doubly-bound -> singly-bound) EGFR_11UL EGFR_11CG transforms in (Cbl bind Grb2 directly) EGFR_11CC EGFR_11CC tranforms in (Cbl-Grb2 loose direct binding, but stay bound to EGFR) EGFR_11CG
Grb2 and EGFR_11CG bind yielding EGFR_11LG EGFR_11LG dissociates to Grb2 and EGFR_11CG Grb2 and EGFR_02UU bind yielding EGFR_02UG EGFR_02UG dissociates to Grb2 and EGFR_02UU
CG and EGFR_02UU bind yielding EGFR_02UL EGFR_02UL dissociates to CG and EGFR_02UU Cbl and EGFR_02UG bind yielding EGFR_02UL EGFR_02UL dissociates to Cbl and EGFR_02UG
Cbl and EGFR_12UU bind yielding EGFR_12CU EGFR_12CU dissociates to Cbl and EGFR_12UU CG and EGFR_12UU bind yielding EGFR_12LU EGFR_12LU dissociates to CG and EGFR_12UU
Grb2 and EGFR_12UU bind yielding EGFR_12UG EGFR_12UG dissociates to Grb2 and EGFR_12UU CG and EGFR_12UU bind yielding EGFR_12UL EGFR_12UL dissociates to CG and EGFR_12UU
Grb2 and EGFR_12CU bind yielding EGFR_12LU EGFR_12LU dissociates to Grb2 and EGFR_12CU Grb2 and EGFR_12CU bind yielding EGFR_12CG EGFR_12CG dissociates to Grb2 and EGFR_12CU
Grb2 and EGFR_12LU bind yielding EGFR_12LG EGFR_12LG dissociates to Grb2 and EGFR_12LU EGFR_12LU transforms in (singly-bound -> doubly-bound) EGFR_12CC EGFR_12CC tranforms in (doubly-bound -> singly-bound) EGFR_12LU
Cbl and EGFR_12UG bind yielding EGFR_12CG EGFR_12CG dissociates to Cbl and EGFR_12UG CG and EGFR_12UG bind yielding EGFR_12LG EGFR_12LG dissociates to CG and EGFR_12UG
Cbl and EGFR_12UG bind yielding EGFR_12UL EGFR_12UL dissociates to Cbl and EGFR_12UG EGFR_12UL transforms in (singly-bound -> doubly-bound) EGFR_12CC EGFR_12CC tranforms in (doubly-bound -> singly-bound) EGFR_12UL
EGFR_12CG transforms in (Cbl bind Grb2 directly) EGFR_12CC EGFR_12CC tranforms in (Cbl-Grb2 loose direct binding, but stay bound to EGFR) EGFR_12CG Grb2 and EGFR_12CG bind yielding EGFR_12LG EGFR_12LG dissociates to Grb2 and EGFR_12CG
Rules
Assignment Rule (variable: kkin) Assignment Rule (variable: K45P) Assignment Rule (variable: KcgP) Assignment Rule (variable: kkin68)
Assignment Rule (variable: kptp68) Assignment Rule (variable: kb45) Assignment Rule (variable: kb68) Assignment Rule (variable: ku68)
Assignment Rule (variable: kbcg) Assignment Rule (variable: ku45M) Assignment Rule (variable: kb45P) Assignment Rule (variable: kb68P)
Assignment Rule (variable: ku68M) Assignment Rule (variable: kucgM) Assignment Rule (variable: kbcgP) Assignment Rule (variable: Tyr)
Assignment Rule (variable: Ub) Assignment Rule (variable: TyrNorm) Assignment Rule (variable: UbNorm)  
Physical entities
Compartments Species
cell Cbl Grb2 CG
Tyr Ub TyrNorm
UbNorm EGFR_00UU EGFR_10UU
EGFR_10CU EGFR_10LU EGFR_01UU
EGFR_01UG EGFR_01UL EGFR_11UU
EGFR_11CU EGFR_11LU EGFR_11UG
EGFR_11UL EGFR_11CG EGFR_11CC
EGFR_11LG EGFR_02UU EGFR_02UG
EGFR_02UL EGFR_12UU EGFR_12CU
EGFR_12LU EGFR_12UG EGFR_12UL
EGFR_12CG EGFR_12CC EGFR_12LG
Global parameters
K45P KcgP kptp68 kkin
kkin68 kb45 ku45M kb45P
kb68 ku68 kb68P ku68M
kbcg kbcgP kucgM Ltot
RT CblT Grb2T kptp
kkinbase nH xT K45
Kcg ku45 kucg PYMax
UbMax floc CblWT CblFactor
Reactions (120)
 
 EGFR_10UU has site Y1045 dephosphorylated [EGFR_10UU] ↔ [EGFR_00UU];   {EGFR_10UU}
 
 EGFR_01UU has site Y1068/Y1086 dephosphorylated [EGFR_01UU] ↔ [EGFR_00UU];   {EGFR_01UU}
 
 EGFR_11UU has site Y1045 dephosphorylated [EGFR_11UU] ↔ [EGFR_01UU];   {EGFR_11UU}
 
 EGFR_11UU has site Y1068/Y1086 dephosphorylated [EGFR_11UU] ↔ [EGFR_10UU];   {EGFR_11UU}
 
 EGFR_11CU has site Y1068/Y1086 dephosphorylated [EGFR_11CU] ↔ [EGFR_10CU];   {EGFR_11CU}
 
 EGFR_11LU has site Y1068/Y1086 dephosphorylated [EGFR_11LU] ↔ [EGFR_10LU];   {EGFR_11LU}
 
 EGFR_11UG has site Y1045 dephosphorylated [EGFR_11UG] ↔ [EGFR_01UG];   {EGFR_11UG}
 
 EGFR_11UL has site Y1045 dephosphorylated [EGFR_11UL] ↔ [EGFR_01UL];   {EGFR_11UL}
 
 EGFR_02UU has site Y1068/Y1086 dephosphorylated [EGFR_02UU] ↔ [EGFR_01UU];   {EGFR_02UU}
 
 EGFR_02UG has site Y1068/Y1-86 dephosphorylated [EGFR_02UG] ↔ [EGFR_01UG];   {EGFR_02UG}
 
 EGFR_02UL has site Y1068/Y1-86 dephosphorylated [EGFR_02UL] ↔ [EGFR_01UL];   {EGFR_02UL}
 
 EGFR_12UU has site Y1045 dephosphorylated [EGFR_12UU] ↔ [EGFR_02UU];   {EGFR_12UU}
 
 EGFR_12UU has site Y1068/Y1086 dephosphorylated [EGFR_12UU] ↔ [EGFR_11UU];   {EGFR_12UU}
 
 EGFR_12CU has site Y1068/Y1086 dephosphorylated [EGFR_12CU] ↔ [EGFR_11CU];   {EGFR_12CU}
 
 EGFR_12LU has site Y1068/Y1086 dephosphorylated [EGFR_12LU] ↔ [EGFR_11LU];   {EGFR_12LU}
 
 EGFR_12UG has site Y1045 dephosphorylated [EGFR_12UG] ↔ [EGFR_02UG];   {EGFR_12UG}
 
 EGFR_12UG has site Y1068/Y1-86 dephosphorylated [EGFR_12UG] ↔ [EGFR_11UG];   {EGFR_12UG}
 
 EGFR_12UL has site Y1045 dephosphorylated [EGFR_12UL] ↔ [EGFR_02UL];   {EGFR_12UL}
 
 EGFR_12UL has site Y1068/Y1-86 dephosphorylated [EGFR_12UL] ↔ [EGFR_11UL];   {EGFR_12UL}
 
 EGFR_12CG has site Y1068/Y1-86 dephosphorylated [EGFR_12CG] ↔ [EGFR_11CG];   {EGFR_12CG}
 
 EGFR_12CC has site Y1068/Y1-86 dephosphorylated [EGFR_12CC] ↔ [EGFR_11CC];   {EGFR_12CC}
 
 EGFR_12LG has site Y1068/Y1-86 dephosphorylated [EGFR_12LG] ↔ [EGFR_11LG];   {EGFR_12LG}
 
 EGFR_00UU has site Y1045 phosphorylated [EGFR_00UU] ↔ [EGFR_10UU];   {EGFR_00UU}
 
 EGFR_00UU has site Y1068/Y1086 phosphorylated [EGFR_00UU] ↔ [EGFR_01UU];   {EGFR_00UU}
 
 EGFR_10UU has site Y1068/Y1086 phosphorylated [EGFR_10UU] ↔ [EGFR_11UU];   {EGFR_10UU}
 
 EGFR_10CU has site Y1068/Y1086 phosphorylated [EGFR_10CU] ↔ [EGFR_11CU];   {EGFR_10CU}
 
 EGFR_10LU has site Y1068/Y1086 phosphorylated [EGFR_10LU] ↔ [EGFR_11LU];   {EGFR_10LU}
 
 EGFR_01UU has site Y1045 phosphorylated [EGFR_01UU] ↔ [EGFR_11UU];   {EGFR_01UU}
 
 EGFR_01UU has site Y1068/Y1086 phosphorylated [EGFR_01UU] ↔ [EGFR_02UU];   {EGFR_01UU}
 
 EGFR_01UG has site Y1045 phosphorylated [EGFR_01UG] ↔ [EGFR_11UG];   {EGFR_01UG}
 
 EGFR_01UG has site Y1068/Y1086 phosphorylated [EGFR_01UG] ↔ [EGFR_02UG];   {EGFR_01UG}
 
 EGFR_01UL has site Y1045 phosphorylated [EGFR_01UL] ↔ [EGFR_11UL];   {EGFR_01UL}
 
 EGFR_01UL has site Y1068/Y1086 phosphorylated [EGFR_01UL] ↔ [EGFR_02UL];   {EGFR_01UL}
 
 EGFR_11UU has site Y1068/Y1086 phosphorylated [EGFR_11UU] ↔ [EGFR_12UU];   {EGFR_11UU}
 
 EGFR_11CU has site Y1068/Y1086 phosphorylated [EGFR_11CU] ↔ [EGFR_12CU];   {EGFR_11CU}
 
 EGFR_11LU has site Y1068/Y1086 phosphorylated [EGFR_11LU] ↔ [EGFR_12LU];   {EGFR_11LU}
 
 EGFR_11UG has site Y1068/Y1086 phosphorylated [EGFR_11UG] ↔ [EGFR_12UG];   {EGFR_11UG}
 
 EGFR_11UL has site Y1068/Y1086 phosphorylated [EGFR_11UL] ↔ [EGFR_12UL];   {EGFR_11UL}
 
 EGFR_11CG has site Y1068/Y1086 phosphorylated [EGFR_11CG] ↔ [EGFR_12CG];   {EGFR_11CG}
 
 EGFR_11CC has site Y1068/Y1086 phosphorylated [EGFR_11CC] ↔ [EGFR_12CC];   {EGFR_11CC}
 
 EGFR_11LG has site Y1068/Y1086 phosphorylated [EGFR_11LG] ↔ [EGFR_12LG];   {EGFR_11LG}
 
 EGFR_02UU has site Y1045 phosphorylated [EGFR_02UU] ↔ [EGFR_12UU];   {EGFR_02UU}
 
 EGFR_02UG has site Y1045 phosphorylated [EGFR_02UG] ↔ [EGFR_12UG];   {EGFR_02UG}
 
 EGFR_02UL has site Y1045 phosphorylated [EGFR_02UL] ↔ [EGFR_12UL];   {EGFR_02UL}
 
 Cbl and Grb2 bind yielding CG [Cbl] + [Grb2] ↔ [CG];   {Cbl} , {Grb2}
 
 CG dissociates to Cbl and Grb2 [CG] ↔ [Cbl] + [Grb2];   {CG}
 
 Cbl and EGFR_10UU bind yielding EGFR_10CU [Cbl] + [EGFR_10UU] ↔ [EGFR_10CU];   {Cbl} , {EGFR_10UU}
 
 EGFR_10CU dissociates to Cbl and EGFR_10UU [EGFR_10CU] ↔ [Cbl] + [EGFR_10UU];   {EGFR_10CU}
 
 CG and EGFR_10UU bind yielding EGFR_10LU [CG] + [EGFR_10UU] ↔ [EGFR_10LU];   {CG} , {EGFR_10UU}
 
 EGFR_10LU dissociates to CG and EGFR_10UU [EGFR_10LU] ↔ [CG] + [EGFR_10UU];   {EGFR_10LU}
 
 Grb2 and EGFR_10CU bind yielding EGFR_10LU [Grb2] + [EGFR_10CU] ↔ [EGFR_10LU];   {Grb2} , {EGFR_10CU}
 
 EGFR_10LU dissociates to Grb2 and EGFR_10CU [EGFR_10LU] ↔ [Grb2] + [EGFR_10CU];   {EGFR_10LU}
 
 Grb2 and EGFR_01UU bind yielding EGFR_01UG [Grb2] + [EGFR_01UU] ↔ [EGFR_01UG];   {Grb2} , {EGFR_01UU}
 
 EGFR_01UG dissociates to Grb2 and EGFR_01UU [EGFR_01UG] ↔ [Grb2] + [EGFR_01UU];   {EGFR_01UG}
 
 CG and EGFR_01UU bind yielding EGFR_01UL [CG] + [EGFR_01UU] ↔ [EGFR_01UL];   {CG} , {EGFR_01UU}
 
 EGFR_01UL dissociates to CG and EGFR_01UU [EGFR_01UL] ↔ [CG] + [EGFR_01UU];   {EGFR_01UL}
 
 Cbl and EGFR_01UG bind yielding EGFR_01UL [Cbl] + [EGFR_01UG] ↔ [EGFR_01UL];   {Cbl} , {EGFR_01UG}
 
 EGFR_01UL dissociates to Cbl and EGFR_01UG [EGFR_01UL] ↔ [Cbl] + [EGFR_01UG];   {EGFR_01UL}
 
 Cbl and EGFR_11UU bind yielding EGFR_11CU [Cbl] + [EGFR_11UU] ↔ [EGFR_11CU];   {Cbl} , {EGFR_11UU}
 
 EGFR_11CU dissociates to Cbl and EGFR_11UU [EGFR_11CU] ↔ [Cbl] + [EGFR_11UU];   {EGFR_11CU}
 
 CG and EGFR_11UU bind yielding EGFR_11LU [CG] + [EGFR_11UU] ↔ [EGFR_11LU];   {CG} , {EGFR_11UU}
 
 EGFR_11LU dissociates to CG and EGFR_11UU [EGFR_11LU] ↔ [CG] + [EGFR_11UU];   {EGFR_11LU}
 
 Grb2 and EGFR_11UU bind yielding EGFR_11UG [Grb2] + [EGFR_11UU] ↔ [EGFR_11UG];   {Grb2} , {EGFR_11UU}
 
 EGFR_11UG dissociates to Grb2 and EGFR_11UU [EGFR_11UG] ↔ [Grb2] + [EGFR_11UU];   {EGFR_11UG}
 
 CG and EGFR_11UU bind yielding EGFR_11UL [CG] + [EGFR_11UU] ↔ [EGFR_11UL];   {CG} , {EGFR_11UU}
 
 EGFR_11UL dissociates to CG and EGFR_11UU [EGFR_11UL] ↔ [CG] + [EGFR_11UU];   {EGFR_11UL}
 
 Grb2 and EGFR_11CU bind yielding EGFR_11LU [Grb2] + [EGFR_11CU] ↔ [EGFR_11LU];   {Grb2} , {EGFR_11CU}
 
 EGFR_11LU dissociates to Grb2 and EGFR_11CU [EGFR_11LU] ↔ [Grb2] + [EGFR_11CU];   {EGFR_11LU}
 
 Grb2 and EGFR_11CU bind yielding EGFR_11CG [Grb2] + [EGFR_11CU] ↔ [EGFR_11CG];   {Grb2} , {EGFR_11CU}
 
 EGFR_11CG dissociates to Grb2 and EGFR_11CU [EGFR_11CG] ↔ [Grb2] + [EGFR_11CU];   {EGFR_11CG}
 
 Grb2 and EGFR_11LU bind yielding EGFR_11LG [Grb2] + [EGFR_11LU] ↔ [EGFR_11LG];   {Grb2} , {EGFR_11LU}
 
 EGFR_11LG dissociates to Grb2 and EGFR_11LU [EGFR_11LG] ↔ [Grb2] + [EGFR_11LU];   {EGFR_11LG}
 
 EGFR_11LU transforms in (singly-bound -> doubly-bound) EGFR_11CC [EGFR_11LU] ↔ [EGFR_11CC];   {EGFR_11LU}
 
 EGFR_11CC tranforms in (doubly-bound -> singly-bound) EGFR_11LU [EGFR_11CC] ↔ [EGFR_11LU];   {EGFR_11CC}
 
 Cbl and EGFR_11UG bind yielding EGFR_11CG [Cbl] + [EGFR_11UG] ↔ [EGFR_11CG];   {Cbl} , {EGFR_11UG}
 
 EGFR_11CG dissociates to Cbl and EGFR_11UG [EGFR_11CG] ↔ [Cbl] + [EGFR_11UG];   {EGFR_11CG}
 
 CG and EGFR_11UG bind yielding EGFR_11LG [CG] + [EGFR_11UG] ↔ [EGFR_11LG];   {CG} , {EGFR_11UG}
 
 EGFR_11LG dissociates to CG and EGFR_11UG [EGFR_11LG] ↔ [CG] + [EGFR_11UG];   {EGFR_11LG}
 
 Cbl and EGFR_11UG bind yielding EGFR_11UL [Cbl] + [EGFR_11UG] ↔ [EGFR_11UL];   {Cbl} , {EGFR_11UG}
 
 EGFR_11UL dissociates to Cbl and EGFR_11UG [EGFR_11UL] ↔ [Cbl] + [EGFR_11UG];   {EGFR_11UL}
 
 EGFR_11UL transforms in (singly-bound -> doubly-bound) EGFR_11CC [EGFR_11UL] ↔ [EGFR_11CC];   {EGFR_11UL}
 
 EGFR_11CC tranforms in (doubly-bound -> singly-bound) EGFR_11UL [EGFR_11CC] ↔ [EGFR_11UL];   {EGFR_11CC}
 
 EGFR_11CG transforms in (Cbl bind Grb2 directly) EGFR_11CC [EGFR_11CG] ↔ [EGFR_11CC];   {EGFR_11CG}
 
 EGFR_11CC tranforms in (Cbl-Grb2 loose direct binding, but stay bound to EGFR) EGFR_11CG [EGFR_11CC] ↔ [EGFR_11CG];   {EGFR_11CC}
 
 Grb2 and EGFR_11CG bind yielding EGFR_11LG [Grb2] + [EGFR_11CG] ↔ [EGFR_11LG];   {Grb2} , {EGFR_11CG}
 
 EGFR_11LG dissociates to Grb2 and EGFR_11CG [EGFR_11LG] ↔ [Grb2] + [EGFR_11CG];   {EGFR_11LG}
 
 Grb2 and EGFR_02UU bind yielding EGFR_02UG [Grb2] + [EGFR_02UU] ↔ [EGFR_02UG];   {Grb2} , {EGFR_02UU}
 
 EGFR_02UG dissociates to Grb2 and EGFR_02UU [EGFR_02UG] ↔ [Grb2] + [EGFR_02UU];   {EGFR_02UG}
 
 CG and EGFR_02UU bind yielding EGFR_02UL [CG] + [EGFR_02UU] ↔ [EGFR_02UL];   {CG} , {EGFR_02UU}
 
 EGFR_02UL dissociates to CG and EGFR_02UU [EGFR_02UL] ↔ [CG] + [EGFR_02UU];   {EGFR_02UL}
 
 Cbl and EGFR_02UG bind yielding EGFR_02UL [Cbl] + [EGFR_02UG] ↔ [EGFR_02UL];   {Cbl} , {EGFR_02UG}
 
 EGFR_02UL dissociates to Cbl and EGFR_02UG [EGFR_02UL] ↔ [Cbl] + [EGFR_02UG];   {EGFR_02UL}
 
 Cbl and EGFR_12UU bind yielding EGFR_12CU [Cbl] + [EGFR_12UU] ↔ [EGFR_12CU];   {Cbl} , {EGFR_12UU}
 
 EGFR_12CU dissociates to Cbl and EGFR_12UU [EGFR_12CU] ↔ [Cbl] + [EGFR_12UU];   {EGFR_12CU}
 
 CG and EGFR_12UU bind yielding EGFR_12LU [CG] + [EGFR_12UU] ↔ [EGFR_12LU];   {CG} , {EGFR_12UU}
 
 EGFR_12LU dissociates to CG and EGFR_12UU [EGFR_12LU] ↔ [CG] + [EGFR_12UU];   {EGFR_12LU}
 
 Grb2 and EGFR_12UU bind yielding EGFR_12UG [Grb2] + [EGFR_12UU] ↔ [EGFR_12UG];   {Grb2} , {EGFR_12UU}
 
 EGFR_12UG dissociates to Grb2 and EGFR_12UU [EGFR_12UG] ↔ [Grb2] + [EGFR_12UU];   {EGFR_12UG}
 
 CG and EGFR_12UU bind yielding EGFR_12UL [CG] + [EGFR_12UU] ↔ [EGFR_12UL];   {CG} , {EGFR_12UU}
 
 EGFR_12UL dissociates to CG and EGFR_12UU [EGFR_12UL] ↔ [CG] + [EGFR_12UU];   {EGFR_12UL}
 
 Grb2 and EGFR_12CU bind yielding EGFR_12LU [Grb2] + [EGFR_12CU] ↔ [EGFR_12LU];   {Grb2} , {EGFR_12CU}
 
 EGFR_12LU dissociates to Grb2 and EGFR_12CU [EGFR_12LU] ↔ [Grb2] + [EGFR_12CU];   {EGFR_12LU}
 
 Grb2 and EGFR_12CU bind yielding EGFR_12CG [Grb2] + [EGFR_12CU] ↔ [EGFR_12CG];   {Grb2} , {EGFR_12CU}
 
 EGFR_12CG dissociates to Grb2 and EGFR_12CU [EGFR_12CG] ↔ [Grb2] + [EGFR_12CU];   {EGFR_12CG}
 
 Grb2 and EGFR_12LU bind yielding EGFR_12LG [Grb2] + [EGFR_12LU] ↔ [EGFR_12LG];   {Grb2} , {EGFR_12LU}
 
 EGFR_12LG dissociates to Grb2 and EGFR_12LU [EGFR_12LG] ↔ [Grb2] + [EGFR_12LU];   {EGFR_12LG}
 
 EGFR_12LU transforms in (singly-bound -> doubly-bound) EGFR_12CC [EGFR_12LU] ↔ [EGFR_12CC];   {EGFR_12LU}
 
 EGFR_12CC tranforms in (doubly-bound -> singly-bound) EGFR_12LU [EGFR_12CC] ↔ [EGFR_12LU];   {EGFR_12CC}
 
 Cbl and EGFR_12UG bind yielding EGFR_12CG [Cbl] + [EGFR_12UG] ↔ [EGFR_12CG];   {Cbl} , {EGFR_12UG}
 
 EGFR_12CG dissociates to Cbl and EGFR_12UG [EGFR_12CG] ↔ [Cbl] + [EGFR_12UG];   {EGFR_12CG}
 
 CG and EGFR_12UG bind yielding EGFR_12LG [CG] + [EGFR_12UG] ↔ [EGFR_12LG];   {CG} , {EGFR_12UG}
 
 EGFR_12LG dissociates to CG and EGFR_12UG [EGFR_12LG] ↔ [CG] + [EGFR_12UG];   {EGFR_12LG}
 
 Cbl and EGFR_12UG bind yielding EGFR_12UL [Cbl] + [EGFR_12UG] ↔ [EGFR_12UL];   {Cbl} , {EGFR_12UG}
 
 EGFR_12UL dissociates to Cbl and EGFR_12UG [EGFR_12UL] ↔ [Cbl] + [EGFR_12UG];   {EGFR_12UL}
 
 EGFR_12UL transforms in (singly-bound -> doubly-bound) EGFR_12CC [EGFR_12UL] ↔ [EGFR_12CC];   {EGFR_12UL}
 
 EGFR_12CC tranforms in (doubly-bound -> singly-bound) EGFR_12UL [EGFR_12CC] ↔ [EGFR_12UL];   {EGFR_12CC}
 
 EGFR_12CG transforms in (Cbl bind Grb2 directly) EGFR_12CC [EGFR_12CG] ↔ [EGFR_12CC];   {EGFR_12CG}
 
 EGFR_12CC tranforms in (Cbl-Grb2 loose direct binding, but stay bound to EGFR) EGFR_12CG [EGFR_12CC] ↔ [EGFR_12CG];   {EGFR_12CC}
 
 Grb2 and EGFR_12CG bind yielding EGFR_12LG [Grb2] + [EGFR_12CG] ↔ [EGFR_12LG];   {Grb2} , {EGFR_12CG}
 
 EGFR_12LG dissociates to Grb2 and EGFR_12CG [EGFR_12LG] ↔ [Grb2] + [EGFR_12CG];   {EGFR_12LG}
 
Rules (19)
 
 Assignment Rule (name: kkin) kkin = kkinbase*Ltot^nH/(Ltot^nH+xT^nH)
 
 Assignment Rule (name: K45P) K45P = K45/floc
 
 Assignment Rule (name: KcgP) KcgP = Kcg/floc
 
 Assignment Rule (name: kkin68) kkin68 = kkin
 
 Assignment Rule (name: kptp68) kptp68 = kptp
 
 Assignment Rule (name: kb45) kb45 = ku45/K45
 
 Assignment Rule (name: kb68) kb68 = kb45
 
 Assignment Rule (name: ku68) ku68 = ku45
 
 Assignment Rule (name: kbcg) kbcg = kucg/Kcg
 
 Assignment Rule (name: ku45M) ku45M = ku45
 
 Assignment Rule (name: kb45P) kb45P = ku45M/K45P
 
 Assignment Rule (name: kb68P) kb68P = kb45P
 
 Assignment Rule (name: ku68M) ku68M = ku45M
 
 Assignment Rule (name: kucgM) kucgM = kucg
 
 Assignment Rule (name: kbcgP) kbcgP = kucgM/KcgP
 
 Assignment Rule (name: Tyr) Tyr = EGFR_10UU+EGFR_10CU+EGFR_10LU+1*(EGFR_01UU+EGFR_01UG+EGFR_01UL)+2*(EGFR_11UU+EGFR_11CU+EGFR_11LU+EGFR_11UG+EGFR_11UL+EGFR_11CG+EGFR_11CC+EGFR_11LG)+2*(EGFR_02UU+EGFR_02UG+EGFR_02UL)+3*(EGFR_12UU+EGFR_12CU+EGFR_12LU+EGFR_12UG+EGFR_12UL+EGFR_12CG+EGFR_12CC+EGFR_12LG)
 
 Assignment Rule (name: Ub) Ub = EGFR_11CC+EGFR_12CC+EGFR_10CU+EGFR_11CU+EGFR_12CU+EGFR_10LU+EGFR_11LU+EGFR_12LU+EGFR_11CG+EGFR_12CG+EGFR_11LG+EGFR_12LG
 
 Assignment Rule (name: TyrNorm) TyrNorm = Tyr/PYMax
 
 Assignment Rule (name: UbNorm) UbNorm = Ub/(UbMax*CblFactor)
 
   cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 Cbl
Compartment: cell
Initial concentration: 2.80975332814237E-5
 
 Grb2
Compartment: cell
Initial concentration: 3.30538809753328
 
 CG
Compartment: cell
Initial concentration: 0.0146119024667186
 
   Tyr
Compartment: cell
 
   Ub
Compartment: cell
 
   TyrNorm
Compartment: cell
 
   UbNorm
Compartment: cell
 
 EGFR_00UU
Compartment: cell
Initial concentration: 0.833
 
   EGFR_10UU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_10CU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_10LU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_01UU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_01UG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_01UL
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11UU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11CU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11LU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11UG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11UL
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11CG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11CC
Compartment: cell
Initial concentration: 0.0
 
   EGFR_11LG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_02UU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_02UG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_02UL
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12UU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12CU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12LU
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12UG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12UL
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12CG
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12CC
Compartment: cell
Initial concentration: 0.0
 
   EGFR_12LG
Compartment: cell
Initial concentration: 0.0
 
Global Parameters (32)
 
   K45P
Value: NaN
 
   KcgP
Value: NaN
 
   kptp68
Value: NaN
 
   kkin
Value: NaN
 
   kkin68
Value: NaN
 
   kb45
Value: NaN
 
   ku45M
Value: NaN
 
   kb45P
Value: NaN
 
   kb68
Value: NaN
 
   ku68
Value: NaN
 
   kb68P
Value: NaN
 
   ku68M
Value: NaN
 
   kbcg
Value: NaN
 
   kbcgP
Value: NaN
 
   kucgM
Value: NaN
 
   Ltot
Constant
 
   RT
Value: 0.833
Constant
 
   CblT
Value: 0.01464
Constant
 
   Grb2T
Value: 3.32
Constant
 
   kptp
Value: 0.016
Constant
 
   kkinbase
Value: 0.0759155
Constant
 
   nH
Value: 1.13
Constant
 
   xT
Value: 4.59181
Constant
 
   K45
Value: 0.201361
Constant
 
   Kcg
Value: 0.006356
Constant
 
   ku45
Value: 0.001011
Constant
 
   kucg
Value: 0.309271
Constant
 
   PYMax
Value: 2.279493223
Constant
 
   UbMax
Value: 0.014306
Constant
 
   floc
Value: 20000.0
Constant
 
   CblWT
Value: 0.01464
Constant
 
   CblFactor
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000594

Curator's comment: (updated: 11 Mar 2016 09:07:21 GMT)

Figure 4a (left) in the paper. Parameter scan over EGF (lTot in model) and plot the values of UbNorm and TyrNorm after 120 seconds of simulation.

The model units for EGF (lTot) are nM (nano Molar), while to compare to experiments we converted them in ng/ml (the conversion factor is 0,17, i.e. 17 nM = 100 ng/ml).
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