BIOMD0000000441
type: SBMLModel
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
time units: time
function def: 130882
name: function_4_7_1
function def: 130870
modified:
  W3 CDTF: Fri Jun 07 12:45:28 BST 2013
reaction: COPASI4
reaction: COPASI5
area units: area
name: function_4_4_1
compartment: 130954
reaction: COPASI2
species: 131050
name: function_4_1_1
substance units: 130930
name: function_4_2_1
species: 130978
name: Sarma2012 - Oscillations in MAPK cascade (S2)
reaction: COPASI11
name: function_4_9_1
species: 131014
species: 131074
is: GO:0000165
name: function_4_5_1
name: function_4_3_1
function def: 130894
species: 131086
units def: 130906
reaction: COPASI8
reaction: COPASI9
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nick
    family: Juty
function def: 130858
species: 130990
species: 131038
is: http://identifiers.org/taxonomy/131567
function def: 130846
length unit: length
is described by: http://identifiers.org/pubmed/22694947
name: function_4_6_1
curated: true
is: MODEL1112190004
function def: 130834
name: function_4_8_1
volume units: 130906
species: 130966
function def: COPASI12
notes: Sarma2012 - Oscillations in MAPK cascade (S2) Two plausible designs (S1 and S2) of coupled positive and negative feedback loops of MAPK cascade has been described in this paper. This model corresponds to model S2 that comprises negative feedback from MK-PP to MKK_PP layer coupled to positive feedback from MK-PP to MKKK-P layer. This model is described in the article: Oscillations in MAPK cascade triggered by two distinct designs of coupled positive and negative feedback loops. Sarma U, Ghosh I. BMC Res Notes. 2012 Jun 13;5:287. Abstract: BACKGROUND: Feedback loops, both positive and negative are embedded in the Mitogen Activated Protein Kinase (MAPK) cascade. In the three layer MAPK cascade, both feedback loops originate from the terminal layer and their sites of action are either of the two upstream layers. Recent studies have shown that the cascade uses coupled positive and negative feedback loops in generating oscillations. Two plausible designs of coupled positive and negative feedback loops can be elucidated from the literature; in one design the positive feedback precedes the negative feedback in the direction of signal flow and vice-versa in another. But it remains unexplored how the two designs contribute towards triggering oscillations in MAPK cascade. Thus it is also not known how amplitude, frequency, robustness or nature (analogous/digital) of the oscillations would be shaped by these two designs. RESULTS: We built two models of MAPK cascade that exhibited oscillations as function of two underlying designs of coupled positive and negative feedback loops. Frequency, amplitude and nature (digital/analogous) of oscillations were found to be differentially determined by each design. It was observed that the positive feedback emerging from an oscillating MAPK cascade and functional in an external signal processing module can trigger oscillations in the target module, provided that the target module satisfy certain parametric requirements. The augmentation of …
function def: 130798
reaction: COPASI10
reaction: COPASI6
reaction: COPASI7
species: 131002
species: 131062
function def: 130822
function def: 130810
name: function_4_10_1
units def: 130930
creator:
  ORG:
    orgname: National Centre for Cell Science
  n:
    given: Uddipan
    family: Sarma
reaction: COPASI3
species: 131026
created:
  W3 CDTF: Mon Mar 18 12:10:14 GMT 2013

COPASI4
type: Reaction
modifier: 075129
fast: false
kinetic law: 131362
modifier: 075117
modifier: 131350
modifier: 075141
reactant: 131302
is version of: GO:0016310
product: 131314
modifier: 131326
modifier: 131338
name: 4
reversible: false
modifier: 075105

130978
type: Species
initial amount: NaN
has only substance units: false
is version of: P04049
boundary condition: false
name: MKKK_P
initial concentration: 0.0
in compartment: 130954
constant: false
is version of: C00562

130954
type: Compartment
is: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartment

131002
type: Species
initial concentration: 0.0
has only substance units: false
is version of: Q02750
name: MKK_P
in compartment: 130954
is version of: C00562
constant: false
boundary condition: false
initial amount: NaN

131398
type: LocalParameter
value: 0.1
name: k4

131386
type: LocalParameter
value: 9.0
name: KI

131374
type: LocalParameter
value: 20.0
name: K4

130990
type: Species
is version of: Q02750
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3999.99961475501
initial amount: NaN
in compartment: 130954
name: MKK

131050
type: Species
has only substance units: false
boundary condition: false
in compartment: 130954
initial concentration: 0.0
is version of: P28482
constant: false
is version of: C00562
initial amount: NaN
name: M_PP

131302
type: SpeciesReference
stoichiometry: 1.0
species: 131002

131314
type: SpeciesReference
stoichiometry: 1.0
species: 131014

131014
type: Species
initial concentration: 0.0
constant: false
boundary condition: false
initial amount: NaN
has only substance units: false
is version of: Q02750
in compartment: 130954
is version of: C00562
name: MKK_PP

COPASI5
type: Reaction
is version of: GO:0016310
modifier: 131446
reactant: 131410
modifier: 131434
modifier: 075166
modifier: 075153
modifier: 075178
name: 7
product: 131422
kinetic law: 131458
reversible: false
fast: false

131038
type: Species
boundary condition: false
name: M_P
in compartment: 130954
has only substance units: false
initial amount: NaN
constant: false
initial concentration: 0.0
is version of: P28482
is version of: C00562

131410
type: SpeciesReference
stoichiometry: 1.0
species: 131026

131026
type: Species
is version of: P28482
constant: false
boundary condition: false
has only substance units: false
initial concentration: 999.999903688753
initial amount: NaN
in compartment: 130954
name: M

131422
type: SpeciesReference
stoichiometry: 1.0
species: 131038

131482
type: LocalParameter
value: 0.1
name: k7

131470
type: LocalParameter
value: 20.0
name: K7

COPASI2
type: Reaction
reactant: 131098
reversible: false
name: 1
kinetic law: 131134
product: 131110
modifier: 131122
modifier: 075043
modifier: 075031
fast: false
is version of: GO:0016310

131098
type: SpeciesReference
stoichiometry: 1.0
species: 130966

130966
type: Species
is version of: P04049
constant: false
boundary condition: false
has only substance units: false
initial concentration: 999.999903688753
initial amount: NaN
in compartment: 130954
name: MKKK

131182
type: LocalParameter
value: 6.0
name: V1

131170
type: LocalParameter
value: 500.0
name: Ka

131158
type: LocalParameter
value: 15.0
name: K1

131146
type: LocalParameter
value: 100.0
name: A

131110
type: SpeciesReference
stoichiometry: 1.0
species: 130978

130930
type: SBMLUnitsDef
unit: 130942
name: substance

130942
type: SBMLUnit
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE

COPASI11
type: Reaction
kinetic law: 131974
name: 10
modifier: 131962
modifier: 131950
product: 131926
fast: false
modifier: 075382
reactant: 131914
reversible: false
modifier: 075370
is version of: GO:0016311
modifier: 075358
modifier: 131938

131998
type: LocalParameter
value: 0.02
name: k10

131986
type: LocalParameter
value: 20.0
name: K10

131926
type: SpeciesReference
stoichiometry: 1.0
species: 131026

131914
type: SpeciesReference
stoichiometry: 1.0
species: 131038

131086
type: Species
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 499.999951844377
initial amount: NaN
in compartment: 130954
name: P3

131074
type: Species
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 499.999951844377
initial amount: NaN
in compartment: 130954
name: P2

130906
type: SBMLUnitsDef
unit: 130918
name: volume

130918
type: SBMLUnit
exponent: 1.0
scale: -3
multipler: 1.0
kind: LITRE

COPASI8
type: Reaction
modifier: 075250
product: 131662
modifier: 131686
name: 5
modifier: 075274
is version of: GO:0016311
reversible: false
fast: false
kinetic law: 131698
modifier: 131674
modifier: 075262
reactant: 131650

131662
type: SpeciesReference
stoichiometry: 1.0
species: 131002

131722
type: LocalParameter
value: 0.02
name: k5

131710
type: LocalParameter
value: 20.0
name: K5

131650
type: SpeciesReference
stoichiometry: 1.0
species: 131014

COPASI9
type: Reaction
name: 6
fast: false
reactant: 131734
product: 131746
modifier: 131770
reversible: false
modifier: 075286
modifier: 075310
modifier: 131758
kinetic law: 131782
is version of: GO:0016311
modifier: 075298

131734
type: SpeciesReference
stoichiometry: 1.0
species: 131002

131746
type: SpeciesReference
stoichiometry: 1.0
species: 130990

131806
type: LocalParameter
value: 0.02
name: k6

131794
type: LocalParameter
value: 20.0
name: K6

COPASI10
type: Reaction
fast: false
name: 9
reactant: 131818
modifier: 075334
modifier: 075322
reversible: false
product: 131830
kinetic law: 131878
modifier: 131842
modifier: 131854
is version of: GO:0016311
modifier: 075346
modifier: 131866

131818
type: SpeciesReference
stoichiometry: 1.0
species: 131050

131830
type: SpeciesReference
stoichiometry: 1.0
species: 131038

131902
type: LocalParameter
value: 0.02
name: k9

131890
type: LocalParameter
value: 20.0
name: K9

COPASI6
type: Reaction
reversible: false
product: 131506
fast: false
modifier: 131530
name: 8
modifier: 075190
modifier: 075214
modifier: 075202
modifier: 131518
kinetic law: 131542
is version of: GO:0016310
reactant: 131494

131506
type: SpeciesReference
stoichiometry: 1.0
species: 131050

131566
type: LocalParameter
value: 0.1
name: k8

131554
type: LocalParameter
value: 20.0
name: K8

131494
type: SpeciesReference
stoichiometry: 1.0
species: 131038

COPASI7
type: Reaction
reactant: 131578
kinetic law: 131614
product: 131590
fast: false
reversible: false
modifier: 075238
name: 2
has version: GO:0016311
modifier: 075226
modifier: 131602

131062
type: Species
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.9999903688752
initial amount: NaN
in compartment: 130954
name: P1

131578
type: SpeciesReference
stoichiometry: 1.0
species: 130978

131638
type: LocalParameter
value: 0.1
name: k2

131626
type: LocalParameter
value: 100.0
name: K2

131590
type: SpeciesReference
stoichiometry: 1.0
species: 130966

COPASI3
type: Reaction
modifier: 075068
is version of: GO:0016310
reactant: 131194
modifier: 131218
name: 3
modifier: 131242
reversible: false
modifier: 131230
product: 131206
modifier: 075093
modifier: 075080
modifier: 075055
fast: false
kinetic law: 131254

131194
type: SpeciesReference
stoichiometry: 1.0
species: 130990

131206
type: SpeciesReference
stoichiometry: 1.0
species: 131002

131290
type: LocalParameter
value: 0.1
name: k3

131278
type: LocalParameter
value: 9.0
name: KI

131266
type: LocalParameter
value: 20.0
name: K3