metaid_0000024
constant: true
value: 5.0
type: Parameter

metaid_0000045
name: dephosphorylation of PP-MAPK
reactant: 079509
product: 079521
is version of: GO:0006470
is version of: http://identifiers.org/ec-code/3.1.3.16
type: Reaction
kinetic law: 079558
fast: false
modifier: 079546
is version of: GO:0000188
modifier: 079533
reversible: false

metaid_0000031
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000028
type: Species

metaid_0000038
unit: 079389
name: nanomole (default)
type: SBMLUnitsDef

metaid_0000028
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

metaid_0000021
constant: true
value: 15.0
type: Parameter

metaid_0000027
constant: true
value: 78.0
type: Parameter

079401
stoichiometry: 1.0
species: metaid_0000029
type: SpeciesReference

079461
stoichiometry: 1.0
species: metaid_0000031
type: SpeciesReference

metaid_0000046
kinetic law: 079618
reactant: 079570
is version of: GO:0006470
is version of: http://identifiers.org/ec-code/3.1.3.16
reversible: false
name: dephosphorylation of P-MAPK
type: Reaction
modifier: 079606
fast: false
modifier: 079594
product: 079582

metaid_0000023
constant: true
value: 0.084
type: Parameter

metaid_0000032
is: Q05116
constant: true
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: metaid_0000028
name: MAPKK1
type: Species

079509
stoichiometry: 1.0
species: metaid_0000031
type: SpeciesReference

metaid_0000022
constant: true
value: 500.0
type: Parameter

BIOMD0000000031
species: metaid_0000132
units def: metaid_0000038
parameter: metaid_0000019
parameter: metaid_0000025
species: metaid_0000032
modified:
  W3 CDTF: Tue May 15 22:43:41 BST 2012
parameter: metaid_0000024
parameter: metaid_0000021
is version of: GO:0000165
is described by: http://identifiers.org/pubmed/14744999
name: Markevich2004_MAPK_orderedMM2kinases
reaction: metaid_0000043
parameter: metaid_0000020
length unit: length
type: SBMLModel
is: MODEL6618738800
parameter: metaid_0000023
species: metaid_0000033
species: metaid_0000030
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nicolas
    family: Le Novère
compartment: metaid_0000028
curated: true
occurs in: http://identifiers.org/taxonomy/8355
area units: area
notes: The model describes the double phosphorylation of MAP kinase by an ordered mechanism using the Michaelis-Menten formalism. Two different enzymes, MAPKK1 and MAPKK2, successively phosphorylate the MAP kinase, but one and the same phosphatase dephosphorylates both sites. The model reproduces figure S9 in the supplemental material of the article. The model is further described in: Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Markevich NI, Hoek JB, Kholodenko BN. J Cell Biol. 2004 Feb 2;164(3):353-9. PMID: 14744999 ; DOI: 10.1083/jcb.200308060 Abstract: Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation. Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase (MKP3) of extracellular signal-regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level. Likewise, a cycle where multisite phosphorylations are performed by different kinases, but dephosphorylation reactions are catalyzed by the same phosphatase, can also exhibit bistability and hysteresis. Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team. For more information see the terms of use . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry …
time units: metaid_0000017
reaction: metaid_0000046
substance units: metaid_0000038
species: metaid_0000031
species: metaid_0000029
created:
  W3 CDTF: Thu Jun 30 11:11:00 BST 2005
parameter: metaid_0000027
parameter: metaid_0000026
reaction: metaid_0000045
volume units: metaid_0000323
parameter: metaid_0000022
reaction: metaid_0000044

079449
stoichiometry: 1.0
species: metaid_0000030
type: SpeciesReference

metaid_0000043
is homolog to: REACT 136
name: phosphorylation of MAPK
is version of: http://identifiers.org/ec-code/2.7.12.2
is version of: GO:0004708
product: 079413
type: Reaction
kinetic law: 079437
is homolog to: REACT 2247
fast: false
reactant: 079401
reversible: false
is version of: GO:0006468
modifier: 079425

metaid_0000026
constant: true
value: 18.0
type: Parameter

079570
stoichiometry: 1.0
species: metaid_0000030
type: SpeciesReference

metaid_0000132
is: Q05116
constant: true
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 1.0
in compartment: metaid_0000028
name: MAPKK2
type: Species

metaid_0000033
is: Q90W58
constant: true
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: metaid_0000028
type: Species

079521
stoichiometry: 1.0
species: metaid_0000030
type: SpeciesReference

079413
stoichiometry: 1.0
species: metaid_0000030
type: SpeciesReference

metaid_0000044
product: 079461
modifier: 079473
is version of: GO:0000187
is homolog to: REACT 2247
fast: false
name: phosphorylation of P-MAPK
reactant: 079449
kinetic law: 079497
reversible: false
is version of: http://identifiers.org/ec-code/2.7.12.2
is version of: GO:0004708
modifier: 079485
type: Reaction
is homolog to: REACT 136

metaid_0000025
constant: true
value: 0.06
type: Parameter

metaid_0000019
constant: true
value: 0.01
type: Parameter

079389
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE
type: SBMLUnit

metaid_0000030
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000028
type: Species

079582
stoichiometry: 1.0
species: metaid_0000029
type: SpeciesReference

metaid_0000020
constant: true
value: 50.0
type: Parameter

metaid_0000029
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 500.0
in compartment: metaid_0000028
type: Species