MODEL8687732743
type: SBMLModel
parameter: 061067
rule: 061030
parameter: 061082
notes: This a model from the article: Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R. Muller M, Obeyesekere M, Mills GB, Ram PT. FASEB J. 2008;22(5):1393-403. 18171696 , Abstract: Activation of the fibroblast growth factor (FGFR) and melanocyte stimulating hormone (MC1R) receptors stimulates B-Raf and C-Raf isoforms that regulate the dynamics of MAPK1,2 signaling. Network topology motifs in mammalian cells include feed-forward and feedback loops and bifans where signals from two upstream molecules integrate to modulate the activity of two downstream molecules. We computationally modeled and experimentally tested signal processing in the FGFR/MC1R/B-Raf/C-Raf/MAPK1,2 network in human melanoma cells; identifying 7 regulatory loops and a bifan motif. Signaling from FGFR leads to sustained activation of MAPK1,2, whereas signaling from MC1R results in transient activation of MAPK1,2. The dynamics of MAPK activation depends critically on the expression level and connectivity to C-Raf, which is critical for a sustained MAPK1,2 response. A partially incoherent bifan motif with a feedback loop acts as a logic gate to integrate signals and regulate duration of activation of the MAPK signaling cascade. Further reducing a 106-node ordinary differential equations network encompassing the complete network to a 6-node network encompassing rate-limiting processes sustains the feedback loops and the bifan, providing sufficient information to predict biological responses. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Muller, Obeyesekere, Mills, Ram. (2008) - version01 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@auckland.ac.nz The University of Auckland Auckland Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomode…
parameter: 061115
parameter: 061112
parameter: 061085
rule: 061036
parameter: 061052
units def: 131497
rule: 061033
parameter: 061061
parameter: 061106
curated: false
volume units: 679943
parameter: 061094
rule: 061042
parameter: 061091
parameter: 061076
name: Muller2008_MAPKactivation_Dynamics
parameter: 061109
units def: 131424
rule: 061039
area units: area
substance units: metaid_0000106
units def: 131546
rule: 061048
parameter: 061121
parameter: 061079
parameter: 061050
parameter: 061058
units def: 131388
compartment: 061028
parameter: 061055
parameter: 061070
parameter: 061124
time units: 131570
units def: 131473
parameter: 061097
parameter: 061103
parameter: 061100
parameter: 061088
parameter: 061073
parameter: 061118
length unit: length
units def: 131570
parameter: 061064
rule: 061031
rule: 061045
is described by: http://identifiers.org/pubmed/18171696
parameter: 061049

061067
type: Parameter
constant: false
units: 131388
value: NaN
name: g2

131388
type: SBMLUnitsDef
unit: 131412
unit: 131400
name: micromolar

131412
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

131400
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

061082
type: Parameter
constant: true
units: 131497
value: 0.6
name: f13

131497
type: SBMLUnitsDef
unit: 131533
unit: 131521
unit: 131509
name: second_order_rate_constant

131533
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

131521
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

131509
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE

061115
type: Parameter
constant: true
units: 131473
value: 1.0
name: d5

131473
type: SBMLUnitsDef
unit: 131485
name: first_order_rate_constant

131485
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

061112
type: Parameter
constant: true
units: 131473
value: 0.1
name: f45

061085
type: Parameter
constant: true
units: 131497
value: 0.1
name: h36

061052
type: Parameter
constant: false
units: 131388
value: NaN
name: g1

061061
type: Parameter
constant: false
units: 131388
value: 0.0
name: y2

061106
type: Parameter
constant: false
units: 131388
value: 0.0
name: y5

061094
type: Parameter
constant: false
units: 131388
value: 0.0
name: y4

061091
type: Parameter
constant: true
units: 131388
value: 10.0
name: E

061076
type: Parameter
constant: false
units: 131388
value: 0.0
name: y3

061109
type: Parameter
constant: true
units: 131473
value: 0.3
name: f35

131424
type: SBMLUnitsDef
unit: 131461
unit: 131449
unit: 131437
name: flux

131461
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

131449
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

131437
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

131546
type: SBMLUnitsDef
unit: 131558
name: minute

131558
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

061121
type: Parameter
constant: true
units: 131497
value: 0.1
name: h36

061079
type: Parameter
constant: true
units: 131497
value: 1.5
name: f53

061050
type: Parameter
constant: true
units: 131424
value: 10.0
name: a1

061058
type: Parameter
constant: true
units: 131473
value: 0.2
name: d1

061028
type: Compartment
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0

061055
type: Parameter
constant: true
units: 131388
value: 10.0
name: b1

061070
type: Parameter
constant: true
units: 131388
value: 10.0
name: b2

061124
type: Parameter
constant: true
units: 131473
value: 0.001
name: d6

131570
type: SBMLUnitsDef
unit: 131583
name: time

131583
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

061097
type: Parameter
constant: true
units: 131473
value: 0.1
name: f14

061103
type: Parameter
constant: true
units: 131473
value: 1.1
name: d4

061100
type: Parameter
constant: true
units: 131473
value: 0.8
name: f24

061088
type: Parameter
constant: true
units: 131473
value: 1.0
name: d3

061073
type: Parameter
constant: true
units: 131473
value: 0.1
name: d2

061118
type: Parameter
constant: false
units: 131388
value: 0.0
name: y6

061064
type: Parameter
constant: true
units: 131424
value: 10.0
name: a2

061049
type: Parameter
constant: false
units: 131388
value: 0.0
name: y1