BIOMD0000000262
type: SBMLModel
reaction: 989951
units def: 594181
modified:
  W3 CDTF: Wed Sep 21 09:39:34 BST 2011
parameter: 989990
species: 989946
rule: 989985
parameter: 990005
species: 989933
units def: 594085
parameter: 989997
species: 989936
rule: 989988
has version: REACT 12464.1
reaction: 989963
reaction: 989953
parameter: 989993
substance units: 594024
is: MODEL1004060001
species: 989941
reaction: 989959
has version: GO:0007173
parameter: 990004
name: Fujita2010_Akt_Signalling_EGF
reaction: 989954
parameter: 989996
creator:
  ORG:
    orgname: University of Tokyo
  n:
    given: Kazuhiro
    family: Fujita
species: 989934
reaction: 989952
units def: 594109
has version: GO:0043491
notes: EGF dependent Akt pathway model made by Kazuhiro A. Fujita. This is the EGF dependent Akt pathway model described in: Decoupling of receptor and downstream signals in the Akt pathway by its low-pass filter characteristics. Fujita KA, Toyoshima Y, Uda S, Ozaki Y, Kubota H, and Kuroda S. Sci Signal. 2010 Jul 27;3(132):ra56. PMID: 20664065 ; DOI: 10.1126/scisignal.2000810 Abstract: In cellular signal transduction, the information in an external stimulus is encoded in temporal patterns in the activities of signaling molecules; for example, pulses of a stimulus may produce an increasing response or may produce pulsatile responses in the signaling molecules. Here, we show how the Akt pathway, which is involved in cell growth, specifically transmits temporal information contained in upstream signals to downstream effectors. We modeled the epidermal growth factor (EGF)–dependent Akt pathway in PC12 cells on the basis of experimental results. We obtained counterintuitive results indicating that the sizes of the peak amplitudes of receptor and downstream effector phosphorylation were decoupled; weak, sustained EGF receptor (EGFR) phosphorylation, rather than strong, transient phosphorylation, strongly induced phosphorylation of the ribosomal protein S6, a molecule downstream of Akt. Using frequency response analysis, we found that a three-component Akt pathway exhibited the property of a low-pass filter and that this property could explain decoupling of the peak amplitudes of receptor phosphorylation and that of downstream effectors. Furthermore, we found that lapatinib, an EGFR inhibitor used as an anticancer drug, converted strong, transient Akt phosphorylation into weak, sustained Akt phosphorylation, and, because of the low-pass filter characteristics of the Akt pathway, this led to stronger S6 phosphorylation than occurred in the absence of the inhibitor. Thus, an EGFR inhibitor can potentially act as a downstream activator of some effectors. The different versions of in…
units def: 594217
parameter: 990003
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occurs in: BTO:0001009
length unit: length
has version: rno04012
units def: 594024
curated: true
reaction: 989958
reaction: 989948
parameter: 989999
units def: 594048
species: 989942
units def: 594157
has version: GO:0071364
created:
  W3 CDTF: Tue Aug 24 12:49:55 BST 2010
volume units: 594109
reaction: 989962
species: 989945
species: 989940
occurs in: http://identifiers.org/taxonomy/10116
species: 989932
parameter: 989991
parameter: 989992
units def: 594133
species: 989939
compartment: 989931
area units: metaid_0000005
reaction: 989957
species: 989935
time units: 594085
parameter: 990002
rule: 989987
reaction: 989964
has version: REACT 9417.3
parameter: 989998
initial assignment: BIOMD0000000262#
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
is described by: http://identifiers.org/pubmed/20664065

989951
type: Reaction
kinetic law: 594363
is version of: GO:0005515
reactant: 594338
is: SBO:0000177
product: 594351
fast: false
reactant: 594326
reversible: true
name: pEGFR+Akt

989969
type: LocalParameter
units: 594133
value: 0.00517473
name: k2

594133
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name: per second

594145
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scale: 0
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kind: SECOND

989968
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value: 1.5543E-5
name: k1

594217
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594338
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989936
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989931
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is version of: GO:0005623
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constant: true
size: 1.0
spatial dimensions: 3.0
name: Cell

594351
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989935
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name: pEGFR_Akt
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594326
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989934
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name: pEGFR
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kind: GRAM

989990
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constant: false
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value: 0.0
name: pEGFR_total

989946
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name: EGF_EGFR
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990005
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value: 3600.0
name: ramp_time

594085
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name: seconds

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989933
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name: EGFR
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is version of: Q9WTS1

989997
type: Parameter
is version of: P62755
is version of: C00562
constant: false
units: 594181
value: 0.0
name: pS6_total

989963
type: Reaction
kinetic law: 594693
product: 594680
reactant: 594667
is version of: GO:0004672
is: SBO:0000179
fast: false
reversible: false
name: EGFR_phosphorylation

989981
type: LocalParameter
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value: 0.0192391
name: k1

594680
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594667
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989953
type: Reaction
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is version of: GO:0030163
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fast: false
reversible: false
name: pEGFR_degradation

989972
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value: 0.0997194
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594423
type: SpeciesReference
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989993
type: Parameter
constant: true
units: 594157
value: 60.0587507734138
name: pAkt_scaleFactor

594157
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name: ng

594169
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kind: GRAM

594024
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name: arbitrary_amount

594036
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kind: DIMENSIONLESS

989941
type: Species
name: pAkt_S6
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in compartment: 989931
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boundary condition: false

989959
type: Reaction
kinetic law: 594615
product: 594602
reactant: 594589
is version of: GO:0004721
is: SBO:0000330
fast: false
reversible: false
name: pS6_dephospho

989979
type: LocalParameter
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value: 0.00113102
name: k1

594602
type: SpeciesReference
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989940
type: Species
initial concentration: NaN
is: SBO:0000252
is version of: P62755
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constant: false
boundary condition: false
name: S6
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594589
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989942
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is version of: P62755
boundary condition: false

990004
type: Parameter
constant: true
units: 594085
value: 60.0
name: pulse_time

989954
type: Reaction
is version of: GO:0005515
fast: false
reactant: 594447
product: 594471
kinetic law: 594484
is: SBO:0000179
name: pAkt+S6
reactant: 594459
is version of: REACT_12442
reversible: true

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989939
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is version of: Q63484
name: pAkt
is: SBO:0000252
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594471
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species: 989941

989974
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units: 594133
value: 5.1794E-15
name: k2

989973
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units: 594217
value: 2.10189E-6
name: k1

594459
type: SpeciesReference
stoichiometry: 1.0
species: 989940

989996
type: Parameter
constant: true
units: 594157
value: 49886.2313741851
name: pS6_scaleFactor

989952
type: Reaction
is version of: GO:0004672
product: 594399
fast: false
is: SBO:0000216
product: 594387
name: Akt_phosphorylation
reactant: 594375
kinetic law: 594411
reversible: false

594399
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594387
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594375
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989970
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name: k1

594109
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name: ml

594121
type: SBMLUnit
exponent: 1.0
scale: -3
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kind: LITRE

990003
type: Parameter
constant: true
units: 594133
value: 1.06386129269658E-4
name: EGFR_turnover

989958
type: Reaction
kinetic law: 594576
product: 594563
reactant: 594550
is version of: GO:0004721
is: SBO:0000330
fast: false
reversible: false
name: pAkt_dephospho

989977
type: LocalParameter
units: 594133
value: 0.0327962
name: k1

594563
type: SpeciesReference
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594550
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species: 989939

989948
type: Reaction
reversible: true
reactant: 594290
is version of: GO:0005515
is: SBO:0000177
product: 594302
kinetic law: 594314
reactant: 594278
is version of: GO:0005154
fast: false
name: EGF+EGFR

594290
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species: 989933

594302
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989966
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989965
type: LocalParameter
value: 0.00673816
name: k1

594278
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989932
type: Species
initial concentration: NaN
is version of: IPR006209
is: SBO:0000252
initial amount: 0.0
name: EGF
constant: false
has only substance units: false
in compartment: 989931
substance units: 594157
boundary condition: true

989999
type: Parameter
constant: true
units: 594181
value: 0.0
name: EGF_conc_impulse

594048
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name: arbitrary_conc

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594061
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kind: DIMENSIONLESS

989962
type: Reaction
kinetic law: 594654
product: 594641
reactant: 594628
is version of: GO:0010467
is: SBO:0000184
fast: false
reversible: false
name: EGFR_synthesis

594641
type: SpeciesReference
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594628
type: SpeciesReference
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989945
type: Species
is version of: Q9WTS1
name: pro_EGFR
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constant: true
initial concentration: NaN
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boundary condition: true

989991
type: Parameter
has version: Q63484
is version of: C00562
constant: false
units: 594181
value: 0.0
name: pAkt_total

989992
type: Parameter
constant: true
units: 594157
value: 1.81734813832032E-4
name: pEGFR_scaleFactor

989957
type: Reaction
is version of: GO:0004672
reversible: false
is: SBO:0000179
name: S6_phosphorylation
product: 594523
product: 594510
reactant: 594497
fast: false
kinetic law: 594536

594523
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594510
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594497
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989976
type: LocalParameter
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value: 0.00121498
name: k1

990002
type: Parameter
constant: true
units: 594181
value: 30.0
name: EGF_conc_ramp

989964
type: Reaction
kinetic law: 594720
reactant: 594707
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
name: EGFR_degradation

594707
type: SpeciesReference
stoichiometry: 1.0
species: 989933

989998
type: Parameter
constant: true
units: 594181
value: 0.0
name: EGF_conc_step