396904
stoichiometry: 1.0
species: 506672
type: SpeciesReference

397085
stoichiometry: 1.0
species: 506492
type: SpeciesReference

397291
stoichiometry: 1.0
species: 506712
type: SpeciesReference

397133
stoichiometry: 1.0
species: 506532
type: SpeciesReference

397266
stoichiometry: 1.0
species: 506532
type: SpeciesReference

815904
value: 150.0
type: LocalParameter

396808
stoichiometry: 1.0
species: 506752
type: SpeciesReference

815893
value: 150.0
type: LocalParameter

metaid_0000049
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: KKK_P_norm
type: Species

815911
value: 150.0
type: LocalParameter

396880
stoichiometry: 1.0
species: 506472
type: SpeciesReference

815919
value: 150.0
type: LocalParameter

397339
stoichiometry: 1.0
species: 506552
type: SpeciesReference

507013
kinetic law: 397013
product: 397001
reactant: 396989
reactant: 396977
is version of: GO:0031434
fast: false
reversible: true
name: binding MAPKK-Pase and PP-MAPKK
type: Reaction

507113
reactant: 397218
product: 397230
reversible: false
fast: false
kinetic law: 397254
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
type: Reaction
product: 397242
name: dephosphorylation of P-MAPK

815905
value: 150.0
type: LocalParameter

815894
value: 150.0
type: LocalParameter

506392
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.0E-4
initial amount: NaN
in compartment: 506358
name: MAPKKK inactivator
type: Species

507133
has version: REACT 495
type: Reaction
is version of: GO:0051019
reactant: 397266
kinetic law: 397303
reversible: true
name: binding PP-MAPKK and P-MAPK
is version of: GO:0031434
product: 397291
reactant: 397278
fast: false
has version: REACT 1780

397363
stoichiometry: 1.0
species: 506552
type: SpeciesReference

815910
value: 150.0
type: LocalParameter

metaid_0000048
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: KK_PP_norm
type: Species

397073
stoichiometry: 1.0
species: 506512
type: SpeciesReference

506372
is version of: IPR003577
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.0E-5
initial amount: NaN
in compartment: 506358
name: MAPKKK activator (Ras)
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815918
value: 150.0
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397230
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species: 506512
type: SpeciesReference

396543
stoichiometry: 1.0
species: 506612
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506592
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.0E-4
initial amount: NaN
in compartment: 506358
name: MAPKK-Pase
type: Species

396977
stoichiometry: 1.0
species: 506492
type: SpeciesReference

506492
is version of: Q05116
constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: Mek1-PP
type: Species

397278
stoichiometry: 1.0
species: 506492
type: SpeciesReference

506993
is version of: http://identifiers.org/ec-code/2.7.11.25
reactant: 396928
fast: false
is version of: GO:0006468
is version of: GO:0004709
kinetic law: 396965
is version of: GO:0000186
product: 396940
is homolog to: REACT 614
type: Reaction
product: 396952
name: phosphorylation of P-MAPKK
reversible: false

396687
stoichiometry: 1.0
species: 506452
type: SpeciesReference

BIOMD0000000009
species: 506692
species: 506712
reaction: 506812
rule: metai0051
rule: met100050
is described by: http://identifiers.org/pubmed/8816754
reaction: 506853
species: 506772
species: 506432
compartment: 506358
area units: area
parameter: metaid_0011050
curated: true
reaction: 507013
created:
  W3 CDTF: Thu Feb 10 23:39:30 GMT 2005
reaction: 506893
reaction: 506993
reaction: 506973
species: 506732
species: 506792
species: 506452
reaction: 507053
reaction: 507033
species: metaid_0000049
species: metaid_0000048
species: 506512
species: 506392
reaction: 507173
species: 506612
species: 506572
reaction: 507153
species: 506472
species: 506412
species: 506372
rule: metaid_0000050
creator:
  ORG:
    orgname: University of Vienna
  n:
    given: Rainer
    family: Machne
reaction: 506873
length unit: length
is version of: GO:0000165
species: 506632
species: 506592
reaction: 506913
species: 506492
type: SBMLModel
reaction: 506833
name: Huang1996 - Ultrasensitivity in MAPK cascade
species: 506552
time units: metaid_0000018
species: metaid_0100049
reaction: 507133
reaction: 507113
rule: metaid_0000052
reaction: 507093
species: 506532
species: 506652
reaction: 507073
reaction: 506953
reaction: 506933
reaction: 507193
notes: Huang1996 - Ultrasensitivity in MAPK cascade The temporal sequence of kinase activation, from MAPKKK (activated RAF) to the final effector MAPK (activated ERK), is described here. It is observed from the model that there is an increase in sensitivity along the levels of the cascade, where the activity of MAPK reaches its maximal before MAPKKK. This model is described in the article: Ultrasensitivity in the mitogen-activated protein kinase cascade. Huang CY, Ferrell JE Jr Proc. Natl. Acad. Sci. U.S.A. 1996:93(19):10078-83 Abstract: The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/ response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another. The species K_PP_norm, KKK_P_norm and KK_PP_norm are the relative concentrations of the active MAPK, MAPKK and MAPKKK, that is the double, or single resp. phophorylated forms divided by the total concentrations of each kinase. For MAPK additionally the also active MAPK divided by the maximal concentration of active MAPK is given by rel_K_PP_max. The parameter K_PP_norm_max, the maximal ratio of active MapK, has to be calculated for each ch…
volume units: volume
occurs in: http://identifiers.org/taxonomy/8355
species: 506752
is: MODEL6615048798
is homolog to: REACT 634
species: metaid_0000047
substance units: metaid_0000046
species: 506672
modified:
  W3 CDTF: Tue Jul 16 11:02:42 BST 2013
units def: metaid_0000046

815895
value: 1000.0
type: LocalParameter

397097
stoichiometry: 1.0
species: 506692
type: SpeciesReference

506973
type: Reaction
product: 396904
fast: false
reversible: true
reactant: 396892
name: binding P-MAPKKK and P-MAPKK
reactant: 396880
is version of: GO:0031434
kinetic law: 396916
is version of: GO:0031435
is homolog to: REACT 143

815913
value: 150.0
type: LocalParameter

metaid_0000047
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: K_PP_norm
type: Species

815902
value: 150.0
type: LocalParameter

397049
stoichiometry: 1.0
species: 506592
type: SpeciesReference

815889
value: 1000.0
type: LocalParameter

506472
is version of: Q05116
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: Mek1-P
type: Species

506572
is: Q90W58
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 506358
name: MAPK-Pase
type: Species

397145
stoichiometry: 1.0
species: 506492
type: SpeciesReference

815896
value: 150.0
type: LocalParameter

506933
kinetic law: 396820
product: 396808
reactant: 396796
reactant: 396784
is version of: GO:0031434
fast: false
reversible: true
name: binding MAPKK-Pase and P-MAPKK
type: Reaction

397001
stoichiometry: 1.0
species: 506732
type: SpeciesReference

506432
is version of: P12965
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: Mos-P
type: Species

397327
stoichiometry: 1.0
species: 506492
type: SpeciesReference

396760
stoichiometry: 1.0
species: 506432
type: SpeciesReference

506452
is version of: Q05116
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.2
initial amount: NaN
in compartment: 506358
name: Mek1
type: Species

815912
value: 1000.0
type: LocalParameter

396615
stoichiometry: 1.0
species: 506632
type: SpeciesReference

396989
stoichiometry: 1.0
species: 506592
type: SpeciesReference

metaid_0000046
unit: 396483
name: micromole
type: SBMLUnitsDef

396555
stoichiometry: 1.0
species: 506372
type: SpeciesReference

397194
stoichiometry: 1.0
species: 506792
type: SpeciesReference

815903
value: 1000.0
type: LocalParameter

506953
name: dephosphorylation of P-MAPKK
product: 396856
fast: false
type: Reaction
is version of: GO:0006470
reversible: false
reactant: 396832
product: 396844
kinetic law: 396868
is version of: http://identifiers.org/ec-code/3.1.3.16

396748
stoichiometry: 1.0
species: 506472
type: SpeciesReference

396856
stoichiometry: 1.0
species: 506592
type: SpeciesReference

396495
stoichiometry: 1.0
species: 506412
type: SpeciesReference

397436
stoichiometry: 1.0
species: 506572
type: SpeciesReference

815908
value: 150.0
type: LocalParameter

507093
kinetic law: 397206
product: 397194
reactant: 397182
reactant: 397170
is version of: GO:0051019
fast: false
reversible: true
name: binding MAPK-Pase and P-MAPK
type: Reaction

506752
has part: Q05116
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: MAPKK-Pase_P-Mek1
type: Species

396699
stoichiometry: 1.0
species: 506432
type: SpeciesReference

396928
stoichiometry: 1.0
species: 506672
type: SpeciesReference

506913
is version of: GO:0006468
is version of: GO:0004709
type: Reaction
is version of: http://identifiers.org/ec-code/2.7.11.25
is homolog to: REACT 614
product: 396760
reactant: 396736
name: phosphorylation of MAPKK
fast: false
product: 396748
reversible: false
kinetic law: 396772

397376
stoichiometry: 1.0
species: 506572
type: SpeciesReference

506792
has only substance units: false
initial amount: NaN
boundary condition: false
name: MAPK-Pase_P-Erk2
has part: P26696
in compartment: 506358
constant: false
initial concentration: 0.0
type: Species
has part: Q90W58

815887
value: 150.0
type: LocalParameter

815897
value: 150.0
type: LocalParameter

507073
reversible: false
name: phosphorylation of MAPK
is version of: GO:0004708
is version of: http://identifiers.org/ec-code/2.7.12.2
reactant: 397121
has version: REACT 2247
fast: false
is version of: GO:0006468
kinetic law: 397158
product: 397145
has version: REACT 136
type: Reaction
product: 397133

506512
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.2
initial amount: NaN
in compartment: 506358
name: Erk2
type: Species

815909
value: 1000.0
type: LocalParameter

396736
stoichiometry: 1.0
species: 506652
type: SpeciesReference

397037
stoichiometry: 1.0
species: 506472
type: SpeciesReference

815890
value: 150.0
type: LocalParameter

506812
kinetic law: 396531
name: binding of MAPKKK activator
reactant: 396507
type: Reaction
is homolog to: REACT 996
product: 396519
fast: false
reversible: true
is version of: GO:0031435
reactant: 396495

506772
boundary condition: false
name: MAPK-Pase_PP-Erk2
initial concentration: 0.0
initial amount: NaN
has only substance units: false
has part: Q90W58
in compartment: 506358
constant: false
type: Species
has part: P26696

396567
stoichiometry: 1.0
species: 506432
type: SpeciesReference

815901
value: 150.0
type: LocalParameter

396603
stoichiometry: 1.0
species: 506392
type: SpeciesReference

506532
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: Erk2-P
type: Species

815914
value: 150.0
type: LocalParameter

397182
stoichiometry: 1.0
species: 506572
type: SpeciesReference

507173
kinetic law: 397400
product: 397388
reactant: 397376
reactant: 397363
is version of: GO:0051019
fast: false
reversible: true
name: binding MAPK-Pase and PP-MAPK
type: Reaction

506853
kinetic law: 396627
product: 396615
reactant: 396603
reactant: 396591
is version of: GO:0031435
fast: false
reversible: true
name: binding of MAPKKK inactivator
type: Reaction

396940
stoichiometry: 1.0
species: 506492
type: SpeciesReference

397121
stoichiometry: 1.0
species: 506692
type: SpeciesReference

815888
value: 150.0
type: LocalParameter

396796
stoichiometry: 1.0
species: 506592
type: SpeciesReference

396519
stoichiometry: 1.0
species: 506612
type: SpeciesReference

506412
is version of: P12965
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.003
initial amount: NaN
in compartment: 506358
name: Mos
type: Species

397315
stoichiometry: 1.0
species: 506712
type: SpeciesReference

507153
is version of: GO:0000187
type: Reaction
has version: REACT 136
reactant: 397315
is version of: GO:0004708
name: phosphorylation of P-MAPK
fast: false
is version of: http://identifiers.org/ec-code/2.7.12.2
product: 397339
reversible: false
is version of: GO:0006468
product: 397327
has version: REACT 2247
kinetic law: 397351

507193
reversible: false
type: Reaction
product: 397436
product: 397424
name: dephosphorylation of PP-MAPK
kinetic law: 397448
is version of: http://identifiers.org/ec-code/3.1.3.16
reactant: 397412
is version of: GO:0006470
is version of: GO:0000188
fast: false

506552
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: Erk2-PP
type: Species

396591
stoichiometry: 1.0
species: 506432
type: SpeciesReference

506833
is version of: http://identifiers.org/ec-code/2.7.11.1
type: Reaction
reversible: false
product: 396555
is version of: GO:0000185
product: 396567
is version of: GO:0008349
fast: false
is homolog to: REACT 525
reactant: 396543
name: MAPKKK activation
kinetic law: 396579

396844
stoichiometry: 1.0
species: 506452
type: SpeciesReference

396663
stoichiometry: 1.0
species: 506412
type: SpeciesReference

397424
stoichiometry: 1.0
species: 506532
type: SpeciesReference

815906
value: 1000.0
type: LocalParameter

506652
initial concentration: 0.0
type: Species
has part: P12965
boundary condition: false
name: P-Mos_Mek1
initial amount: NaN
in compartment: 506358
constant: false
has part: Q05116
has only substance units: false

506632
has part: P12965
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: E2_Mos-P
type: Species

396639
stoichiometry: 1.0
species: 506632
type: SpeciesReference

815891
value: 150.0
type: LocalParameter

506692
type: Species
initial amount: NaN
boundary condition: false
name: PP-Mek1_Erk2
has only substance units: false
has part: P26696
has part: Q05116
constant: false
in compartment: 506358
initial concentration: 0.0

506873
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
reactant: 396639
type: Reaction
reversible: false
is version of: GO:0051390
fast: false
name: MAPKKK inactivation
kinetic law: 396675
product: 396651
product: 396663

396483
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

507053
reactant: 397073
reactant: 397085
fast: false
type: Reaction
name: binding MAPK and PP-MAPKK
is version of: GO:0031434
kinetic law: 397109
has version: REACT 495
product: 397097
is version of: GO:0051019
reversible: true
has version: REACT 1780

metaid_0100049
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: relative maximal K_PP
type: Species

396712
stoichiometry: 1.0
species: 506652
type: SpeciesReference

397218
stoichiometry: 1.0
species: 506792
type: SpeciesReference

507033
is version of: GO:0051389
name: dephosphorylation of PP-MAPKK
product: 397037
reversible: false
kinetic law: 397061
fast: false
type: Reaction
product: 397049
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
reactant: 397025

506612
constant: false
name: E1_Mos
boundary condition: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
has only substance units: false
has part: IPR003577
has part: P12965
type: Species

397388
stoichiometry: 1.0
species: 506772
type: SpeciesReference

506672
name: P-Mos_P-Mek1
constant: false
boundary condition: false
has only substance units: false
initial amount: NaN
has part: Q05116
initial concentration: 0.0
has part: P12965
in compartment: 506358
type: Species

metaid_0011050
notes: the maximal value of K_PP_norm at a stimulation conc. of 10.
constant: true
value: 0.900049
type: Parameter

815899
value: 1000.0
type: LocalParameter

815892
value: 1000.0
type: LocalParameter

397242
stoichiometry: 1.0
species: 506572
type: SpeciesReference

815907
value: 150.0
type: LocalParameter

397170
stoichiometry: 1.0
species: 506532
type: SpeciesReference

397025
stoichiometry: 1.0
species: 506732
type: SpeciesReference

506893
type: Reaction
product: 396712
is homolog to: REACT 143
kinetic law: 396724
is version of: GO:0031435
reactant: 396699
fast: false
is version of: GO:0031434
reactant: 396687
reversible: true
name: binding P-MAPKKK and MAPKK

397412
stoichiometry: 1.0
species: 506772
type: SpeciesReference

506732
has part: Q05116
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: MAPKK-Pase_PP-Mek1
type: Species

815886
value: 1000.0
type: LocalParameter

396832
stoichiometry: 1.0
species: 506752
type: SpeciesReference

396651
stoichiometry: 1.0
species: 506392
type: SpeciesReference

815916
value: 1000.0
type: LocalParameter

506358
constant: true
size: 4.0E-12
spatial dimensions: 3.0
type: Compartment

396507
stoichiometry: 1.0
species: 506372
type: SpeciesReference

396952
stoichiometry: 1.0
species: 506432
type: SpeciesReference

506712
boundary condition: false
constant: false
has part: P26696
name: PP-Mek1_P-Erk2
type: Species
has only substance units: false
in compartment: 506358
initial concentration: 0.0
initial amount: NaN
has part: Q05116

396784
stoichiometry: 1.0
species: 506472
type: SpeciesReference

396892
stoichiometry: 1.0
species: 506432
type: SpeciesReference