BIOMD0000000314
type: SBMLModel
creator:
  ORG:
    orgname: German Cancer Research Center
  n:
    given: Marcel
    family: Schilling
rule: 821085
parameter: 821093
parameter: 821103
curated: true
name: Raia2011_IL13_L1236
species: 821057
is version of: GO:0007259
species: 821051
occurs in: http://identifiers.org/taxonomy/9606
reaction: 821073
parameter: 821094
reaction: 821067
reaction: 821074
parameter: 821097
reaction: 821071
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
species: 821049
area units: area
species: 821054
length unit: length
parameter: 821087
reaction: 821063
occurs in: BTO:0004973
species: 821044
parameter: 821100
reaction: 821066
species: 821053
notes: This is the model of IL13 induced signalling in L1236 cells described in the article: Dynamic Mathematical Modeling of IL13-Induced Signaling in Hodgkin and Primary Mediastinal B-Cell Lymphoma Allows Prediction of Therapeutic Targets. Raia V, Schilling M, Böhm M, Hahn B, Kowarsch A, Raue A, Sticht C, Bohl S, Saile M, Möller P, Gretz N, Timmer J, Theis F, Lehmann WD, Lichter P and Klingmüller U. Cancer Res. 2011 Feb 1;71(3):693-704. PubmedID: 21127196 ; DOI: 10.1158/0008-5472.CAN-10-2987 Abstract: Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of JAK (Janus kinase)/STAT signaling pathway. Because of complex, nonlinear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. We report the development of dynamic pathway models based on quantitative data collected on signaling components of JAK/STAT pathway in two lymphoma-derived cell lines, MedB-1 and L1236, representative of PMBL and cHL, respectively. We show that the amounts of STAT5 and STAT6 are higher whereas those of SHP1 are lower in the two lymphoma cell lines than in normal B cells. Distinctively, L1236 cells harbor more JAK2 and less SHP1 molecules per cell than MedB-1 or control cells. In both lymphoma cell lines, we observe interleukin-13 (IL13)-induced activation of IL4 receptor α, JAK2, and STAT5, but not of STAT6. Genome-wide, 11 early and 16 sustained genes are upregulated by IL13 in both lymphoma cell lines. Specifically, the known STAT-inducible negative regulators CISH and SOCS3 are upregulated within 2 hours in MedB-1 but not in L1236 cells. On the basis of this detailed quantitative information, we established two mathematical models, MedB-1 and L1236 model, able to describe the respective experimental data. Most of the model parameters are identifiable and therefore the models are predictive. Sensitivity analysis of the model identifies six possible the…
modified:
  W3 CDTF: Fri Jun 07 16:08:38 BST 2013
species: 821059
parameter: 821096
is version of: REACT_22232
reaction: 821070
created:
  W3 CDTF: Mon Feb 14 03:36:22 GMT 2011
parameter: 821091
reaction: 821069
is described by: http://identifiers.org/pubmed/21127196
is version of: hsa04630
reaction: 821061
parameter: 821099
compartment: 821042
species: 821046
occurs in: C81
species: 821060
reaction: 821062
species: 821056
species: 821050
parameter: 821089
reaction: 821065
parameter: 821102
parameter: 821090
is: MODEL1102020002
reaction: 821075
species: 821047

821093
type: Parameter
is: SBO:0000356
constant: true
value: 0.417538

821103
type: Parameter
is: SBO:0000035
constant: true
value: 0.0115928

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type: SBMLUnitsDef
name: cell_volumes

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exponent: 1.0
scale: -15
multipler: 60.0
kind: LITRE

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boundary condition: false
in compartment: 821042
is: SBO:0000252
name: pSTAT5
constant: false

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type: Compartment
is version of: BTO:0001518
is version of: GO:0005623
is: SBO:0000290
constant: true
size: 100.0
spatial dimensions: 3.0
name: cell

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name: JAK2
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constant: false
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has only substance units: false
boundary condition: false
initial concentration: 24.0
initial amount: NaN

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type: Reaction
is: SBO:0000216
fast: false
reversible: false

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name: STAT5
in compartment: 821042
is: SBO:0000252
constant: false
boundary condition: false
initial amount: NaN
initial concentration: 209.0
has only substance units: false
is version of: P51692
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821094
type: Parameter
is: SBO:0000035
constant: true
value: 0.259686

821067
type: Reaction
is: SBO:0000216
fast: false
reversible: false

821049
type: Species
has version: C00562
has part: MOD:00048
has part: P29597
has version: P78552
constant: false
name: p_IL13_Rec
initial amount: NaN
boundary condition: false
is: SBO:0000297
in compartment: 821042
has part: P35225
has version: P24394
initial concentration: 0.0
has only substance units: false
has part: GO:0016516

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821074
type: Reaction
is: SBO:0000330
fast: false
reversible: false

821054
type: Species
in compartment: 821042
initial concentration: 9.4
is: SBO:0000252
constant: false
boundary condition: false
has only substance units: false
is version of: P29350
initial amount: NaN
name: SHP1

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821097
type: Parameter
is: SBO:0000036
constant: true
value: 0.300019

821071
type: Reaction
is: SBO:0000330
fast: false
reversible: false

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type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM

821087
type: Parameter
is version of: P35225
is: SBO:0000228
constant: true
value: 1.0
name: IL13stimulation

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name: ng_per_ml

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multipler: 1.0
kind: GRAM

821063
type: Reaction
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fast: false
reversible: false

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821044
type: Species
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initial amount: NaN
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in compartment: 821042
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constant: false
has property: GO:0019973
is: SBO:0000297
initial concentration: 1.8
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has only substance units: false
initial concentration: 118.598
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is version of: GO:0016516
name: Rec_i
initial amount: NaN
is: SBO:0000297
constant: false
has part: P29597
has property: GO:0031623
boundary condition: false

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exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

821100
type: Parameter
is: SBO:0000036
constant: true
value: 0.00426767

821066
type: Reaction
is: SBO:0000216
fast: false
reversible: false

821047
type: Species
has part: P29597
has version: P78552
name: IL13_Rec
constant: false
boundary condition: false
initial amount: NaN
in compartment: 821042
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is: SBO:0000297
initial concentration: 0.0
has only substance units: false
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821059
type: Species
initial concentration: 0.0
is: CHEBI:33699
boundary condition: false
has only substance units: false
name: CD274mRNA
initial amount: NaN
encodes: P20963
in compartment: 821042
constant: false
is version of: C00046
is: SBO:0000250

821096
type: Parameter
is: SBO:0000035
constant: true
value: 0.0039243

821070
type: Reaction
is: SBO:0000179
fast: false
reversible: false

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821050
type: Species
has version: P24394
initial concentration: 0.0
initial amount: NaN
constant: false
name: p_IL13_Rec_i
has part: MOD:00048
has part: P29597
boundary condition: false
has part: P35225
is version of: GO:0016516
in compartment: 821042
has property: GO:0031623
has only substance units: false
has version: P78552
is: SBO:0000297

821091
type: Parameter
is: SBO:0000035
constant: true
value: 0.324132

821069
type: Reaction
is: SBO:0000185
fast: false
reversible: false

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stoichiometry: 1.0
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stoichiometry: 1.0
species: 821049

821061
type: Reaction
is: SBO:0000177
fast: false
reversible: false

821060
type: Species
boundary condition: true
is: SBO:0000252
constant: false
has property: GO:0005144
in compartment: 821042
name: IL13
initial concentration: NaN
has only substance units: false
initial amount: NaN
is version of: P35225

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species: 821044

821099
type: Parameter
is: SBO:0000036
constant: true
value: 0.0981611

821062
type: Reaction
is: SBO:0000185
fast: false
reversible: false

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821089
type: Parameter
is: SBO:0000339
constant: true
value: 0.00174087

821065
type: Reaction
is: SBO:0000216
fast: false
reversible: false

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821102
type: Parameter
is: SBO:0000036
constant: true
value: 0.0116389

821090
type: Parameter
is: SBO:0000036
constant: true
value: 9.07541

821075
type: Reaction
is: SBO:0000183
fast: false
reversible: false

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