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notes: Neves2008 - Role of cell shape and size in controlling intracellular signalling The role of cell shape and size in the flow of spatial information from the cell surface receptor to downstream components within the cell has been studied on the β-adrenergic receptor to MAPK-signalling network. This model is described in the article: Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R Cell. 2008, 133(4):666-680 Abstract: The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the beta-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells. This model is hosted on BioModels Database and identified by: MODEL8609366518 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rig…
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metaid_0000106
is version of: http://identifiers.org/ec-code/3.1.4.17
reversible: true
kinetic law: 096747
type: Reaction
fast: false
is version of: GO:0004115
name: pde4_p
modifier: 096735
reactant: 096711
product: 096723

098072
stoichiometry: 1.0
species: metaid_0000064
type: SpeciesReference

metaid_0000077
boundary condition: false
initial concentration: 0.0
has part: P49445
has part: A1L1M0
type: Species
has only substance units: false
constant: false
substance units: metaid_0000006
initial amount: NaN
in compartment: metaid_0000046

098000
units: metaid_0000015
value: 0.5
type: LocalParameter

metaid_0000028
constant: true
units: metaid_0000012
value: 0.2
type: Parameter

096759
units: metaid_0000015
value: 1.3
type: LocalParameter

metaid_0000039
constant: false
units: metaid_0000014
value: NaN
type: Parameter

097855
units: metaid_0000016
value: 0.0059
type: LocalParameter

096229
exponent: 3.0
scale: 0
multipler: 1.0E-6
kind: METRE
type: SBMLUnit

096241
exponent: 2.0
scale: -6
multipler: 1.0
kind: METRE
type: SBMLUnit

098625
stoichiometry: 1.0
species: metaid_0000061
type: SpeciesReference

098253
units: metaid_0000015
value: 0.46
type: LocalParameter

096831
stoichiometry: 1.0
species: metaid_0000060
type: SpeciesReference

metaid_0000122
reversible: true
product: 097831
is version of: GO:0030552
name: B1
reactant: 097807
fast: false
type: Reaction
reactant: 097819
kinetic law: 097843
is version of: GO:0034199

096904
units: metaid_0000012
value: 0.2
type: LocalParameter

098469
stoichiometry: 1.0
species: metaid_0000077
type: SpeciesReference

097434
units: metaid_0000016
value: 10.0
type: LocalParameter

metaid_0000107
reactant: 096771
modifier: 096795
is version of: GO:0004721
kinetic law: 096807
name: PPase_Raf
reversible: true
fast: false
type: Reaction
is version of: http://identifiers.org/ec-code/3.1.3.16
product: 096783

metaid_0000078
is version of: GO:0005952
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000046
type: Species

096542
exponent: 1.0
scale: 0
multipler: 1000.0
kind: DIMENSIONLESS
type: SBMLUnit

metaid_0000117
reactant: 097470
is version of: GO:0034199
fast: false
reversible: true
reactant: 097458
type: Reaction
is version of: GO:0030552
name: A2
product: 097482
kinetic law: 097494

metaid_0000036
constant: true
units: metaid_0000012
value: 1.06
type: Parameter

097109
stoichiometry: 1.0
species: metaid_0000069
type: SpeciesReference

metaid_0000056
type: Species
initial concentration: 3010000.0
has only substance units: false
initial amount: NaN
constant: false
in compartment: metaid_0000046
boundary condition: false
is: CHEBI:15422
is: C00002
substance units: metaid_0000006

metaid_0000136
type: Reaction
kinetic law: 098782
product: 098770
reactant: 098758
reversible: true
is version of: GO:0030552
name: A1
is version of: GO:0034199
reactant: 098746
fast: false

097253
stoichiometry: 1.0
species: metaid_0000050
type: SpeciesReference

098205
stoichiometry: 1.0
species: metaid_0000064
type: SpeciesReference

097518
units: metaid_0000012
value: 0.0167
type: LocalParameter

096469
exponent: -3.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

metaid_0000121
kinetic law: 097771
modifier: 097759
product: 097746
reactant: 097734
is version of: GO:0007190
fast: false
reversible: true
name: AC_basal
type: Reaction

097867
units: metaid_0000012
value: 2.8E-4
type: LocalParameter

metaid_0000108
kinetic law: 096867
product: 096855
reactant: 096843
reactant: 096831
is version of: GO:0031697
fast: false
reversible: true
name: iso_binds_BAR
type: Reaction

metaid_0000079
is version of: GO:0005952
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000046
type: Species

098060
units: metaid_0000015
value: 0.15909
type: LocalParameter

metaid_0000037
constant: false
units: metaid_0000014
value: NaN
type: Parameter

metaid_0000118
name: highKM_PDE
is version of: http://identifiers.org/ec-code/3.1.4.17
kinetic law: 097566
type: Reaction
fast: false
reactant: 097530
product: 097542
is version of: GO:0004115
modifier: 097554
reversible: true

metaid_0000135
reactant: 098686
modifier: 098710
name: PPase_mek
kinetic law: 098722
type: Reaction
product: 098698
fast: false
reversible: true
is version of: GO:0000188
is version of: http://identifiers.org/ec-code/3.1.3.16

metaid_0000057
in compartment: metaid_0000048
has part: P26769
has part: IPR001054
substance units: metaid_0000006
has part: A1L1M0
boundary condition: false
initial concentration: 0.0
type: Species
has only substance units: false
initial amount: NaN
constant: false

097746
stoichiometry: 1.0
species: metaid_0000083
type: SpeciesReference

096891
units: metaid_0000016
value: 1.0
type: LocalParameter

metaid_0000120
kinetic law: 097686
product: 097674
reactant: 097662
reactant: 097650
is version of: GO:0007190
fast: false
reversible: true
name: AC_activation
type: Reaction

metaid_0000044
constant: true
units: metaid_0000012
value: 5.0
type: Parameter

metaid_0000130
reactant: 098349
name: PPase_MAPK
product: 098361
is version of: http://identifiers.org/ec-code/3.1.3.16
modifier: 098373
reversible: true
type: Reaction
kinetic law: 098385
is version of: GO:0000188
fast: false

metaid_0000034
constant: true
units: metaid_0000012
value: 0.1
type: Parameter

096639
stoichiometry: 1.0
species: metaid_0000068
type: SpeciesReference

097049
stoichiometry: 1.0
species: metaid_0000075
type: SpeciesReference

097361
units: metaid_0000012
value: 0.0
type: LocalParameter

097650
stoichiometry: 1.0
species: metaid_0000052
type: SpeciesReference

metaid_0000115
kinetic law: 097337
product: 097325
reactant: 097313
reactant: 097301
is part of: GO:0031684
fast: false
reversible: true
name: trimer
type: Reaction

096494
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

096916
stoichiometry: 1.0
species: metaid_0000083
type: SpeciesReference

096253
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

098157
stoichiometry: 1.0
species: metaid_0000079
type: SpeciesReference

metaid_0000072
initial concentration: 3010000.0
in compartment: metaid_0000046
initial amount: NaN
substance units: metaid_0000006
type: Species
is: C00020
constant: false
is: CHEBI:16027
boundary condition: false
has only substance units: false

096579
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

metaid_0000045
constant: false
units: metaid_0000014
value: NaN
type: Parameter

096603
exponent: -2.0
scale: -6
multipler: 1.0
kind: METRE
type: SBMLUnit

metaid_0000035
constant: false
units: metaid_0000014
value: NaN
type: Parameter

097602
stoichiometry: 1.0
species: metaid_0000077
type: SpeciesReference

097831
stoichiometry: 1.0
species: metaid_0000078
type: SpeciesReference

098409
stoichiometry: 1.0
species: metaid_0000085
type: SpeciesReference

metaid_0000116
kinetic law: 097409
product: 097397
reactant: 097385
reactant: 097373
is version of: GO:0032795
fast: false
reversible: true
name: G_binds_iso_BAR
type: Reaction

096313
exponent: -3.0
scale: -6
multipler: 1.0
kind: METRE
type: SBMLUnit

098217
stoichiometry: 1.0
species: metaid_0000075
type: SpeciesReference

097349
units: metaid_0000016
value: 6.0
type: LocalParameter

097289
units: metaid_0000012
value: 0.0
type: LocalParameter

metaid_0000073
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 0.602
initial amount: NaN
in compartment: metaid_0000046
type: Species

098541
stoichiometry: 1.0
species: metaid_0000054
type: SpeciesReference

097927
units: metaid_0000011
value: 0.0
type: LocalParameter

metaid_0000046
is: GO:0005737
constant: true
size: 1.0
spatial dimensions: 3.0
name: cyto
type: Compartment

098313
units: metaid_0000011
value: 0.0
type: LocalParameter

097373
stoichiometry: 1.0
species: metaid_0000063
type: SpeciesReference

097458
stoichiometry: 1.0
species: metaid_0000080
type: SpeciesReference

097037
units: metaid_0000012
value: 0.25
type: LocalParameter

metaid_0000132
kinetic law: 098505
modifier: 098493
product: 098481
reactant: 098469
fast: false
reversible: true
name: pp_ptp
type: Reaction

098085
stoichiometry: 1.0
species: metaid_0000075
type: SpeciesReference

metaid_0000032
constant: false
units: metaid_0000014
value: NaN
type: Parameter

097061
stoichiometry: 1.0
species: metaid_0000064
type: SpeciesReference

098661
units: metaid_0000016
value: 0.3
type: LocalParameter

097542
stoichiometry: 1.0
species: metaid_0000072
type: SpeciesReference

096265
exponent: 2.0
scale: -6
multipler: 1.0
kind: METRE
type: SBMLUnit

098601
stoichiometry: 1.0
species: metaid_0000060
type: SpeciesReference

metaid_0000084
has part: P49445
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 60.2
initial amount: NaN
in compartment: metaid_0000046
type: Species

098145
stoichiometry: 1.0
species: metaid_0000083
type: SpeciesReference

metaid_0000113
is version of: http://identifiers.org/ec-code/4.6.1.1
product: 097181
reactant: 097169
is version of: GO:0006171
kinetic law: 097205
modifier: 097193
reversible: true
type: Reaction
name: AC_active
fast: false

096627
stoichiometry: 1.0
species: metaid_0000063
type: SpeciesReference

097662
stoichiometry: 1.0
species: metaid_0000071
type: SpeciesReference

metaid_0000074
is version of: Q64623
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 60.2
initial amount: NaN
in compartment: metaid_0000046
type: Species

098517
units: metaid_0000015
value: 6.0
type: LocalParameter

096928
stoichiometry: 1.0
species: metaid_0000072
type: SpeciesReference

096591
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

096723
stoichiometry: 1.0
species: metaid_0000072
type: SpeciesReference

096567
exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

metaid_0000131
kinetic law: 098445
modifier: 098433
product: 098421
reactant: 098409
is version of: GO:0006470
fast: false
reversible: true
name: pp2a_4
type: Reaction

096615
stoichiometry: 1.0
species: metaid_0000081
type: SpeciesReference

096651
stoichiometry: 1.0
species: metaid_0000052
type: SpeciesReference

metaid_0000033
constant: false
units: metaid_0000014
value: NaN
type: Parameter

metaid_0000085
constant: false
initial concentration: 0.0
has only substance units: false
in compartment: metaid_0000046
substance units: metaid_0000006
is version of: P54748
is version of: IPR003607
initial amount: NaN
type: Species
boundary condition: false

metaid_0000114
kinetic law: 097265
product: 097253
reactant: 097241
is version of: GO:0003924
fast: false
reversible: true
name: GTPase
type: Reaction

097277
units: metaid_0000012
value: 0.06667
type: LocalParameter

096988
stoichiometry: 1.0
species: metaid_0000068
type: SpeciesReference

metaid_0000075
is version of: P63086
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 216.72
initial amount: NaN
in compartment: metaid_0000046
type: Species

096301
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

metaid_0000047
is: GO:0005576
constant: true
size: 0.111111111111111
spatial dimensions: 3.0
name: extra
type: Compartment

orgname: California Institute of Technology

W3 CDTF: Wed Aug 20 10:35:11 BST 2008

W3 CDTF: Wed Jun 05 12:00:34 BST 2013

n:
  given: Harish
  family: Dharuri