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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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is version of: GO:0004674
name: PKA_activates_Raf
fast: false
modifier: 097133
product: 097121
reversible: true

097157
type: LocalParameter
units: metaid_0000015
value: 0.5

097109
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000069

097121
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000067

metaid_0000123
type: Reaction
kinetic law: 097915
modifier: 097903
product: 097891
reactant: 097879
is version of: GO:0004703
fast: false
reversible: true
name: GRK

097939
type: LocalParameter
units: metaid_0000017
value: 15.0

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

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

097927
type: LocalParameter
units: metaid_0000011
value: 0.0

097891
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000054

metaid_0000054
type: Species
has part: P18090
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000048

097879
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000063

metaid_0000133
type: Reaction
kinetic law: 098565
modifier: 098553
product: 098541
reactant: 098529
is version of: GO:0004703
fast: false
reversible: true
name: GRK_bg

098589
type: LocalParameter
units: metaid_0000017
value: 4.0

098577
type: LocalParameter
units: metaid_0000011
value: 0.0

098541
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000054

098529
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000063

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

098806
type: LocalParameter
units: metaid_0000012
value: 0.0167

098794
type: LocalParameter
units: metaid_0000016
value: 8.35

098770
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000080

metaid_0000080
type: Species
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

098758
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000083

098746
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000079

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

098517
type: LocalParameter
units: metaid_0000015
value: 6.0

metaid_0000084
type: Species
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

098481
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000076

098469
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000077

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

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

098349
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000064

098361
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000075

098397
type: LocalParameter
units: metaid_0000015
value: 0.77

metaid_0000043
type: Parameter
constant: false
units: metaid_0000010
value: NaN

metaid_0000018
type: Parameter
constant: true
units: metaid_0000009
value: 0.00166112956810631

metaid_0000026
type: Parameter
constant: false
units: metaid_0000010
value: NaN

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

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

metaid_0000022
type: Parameter
constant: false
units: metaid_0000014
value: NaN

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

metaid_0000040
type: Parameter
constant: false
units: metaid_0000014
value: NaN

metaid_0000027
type: Parameter
constant: false
units: metaid_0000014
value: NaN

metaid_0000023
type: Parameter
constant: false
units: metaid_0000014
value: NaN

metaid_0000031
type: Parameter
constant: false
units: metaid_0000010
value: NaN

metaid_0000041
type: Parameter
constant: true
units: metaid_0000012
value: 5.0

metaid_0000106
type: Reaction
is version of: http://identifiers.org/ec-code/3.1.4.17
reversible: true
kinetic law: 096747
fast: false
is version of: GO:0004115
name: pde4_p
modifier: 096735
reactant: 096711
product: 096723

096759
type: LocalParameter
units: metaid_0000015
value: 1.3

096711
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000083

096723
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000072

metaid_0000020
type: Parameter
constant: true
units: metaid_0000012
value: 5.0

metaid_0000113
type: Reaction
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
name: AC_active
fast: false

097181
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000083

097169
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000056

097229
type: LocalParameter
units: metaid_0000015
value: 32.0

097217
type: LocalParameter
units: metaid_0000011
value: 0.0

metaid_0000060
type: Species
is version of: P18090
constant: false
boundary condition: false
has only substance units: false
substance units: metaid_0000006
initial concentration: 94.0
initial amount: NaN
in compartment: metaid_0000048

metaid_0000134
type: Reaction
kinetic law: 098637
product: 098625
reactant: 098613
reactant: 098601
is version of: GO:0032795
fast: false
reversible: true
name: G_binds_BAR

098674
type: LocalParameter
units: metaid_0000012
value: 0.1

098661
type: LocalParameter
units: metaid_0000016
value: 0.3

098649
type: LocalParameter
units: metaid_0000011
value: 0.0

098625
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000061

098613
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000051

098601
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000060

metaid_0000124
type: Reaction
product: 097963
reversible: true
kinetic law: 097988
is version of: http://identifiers.org/ec-code/2.7.11.11
name: PKA_P_PDE
reactant: 097951
is version of: GO:0004674
modifier: 097975
fast: false

097963
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000085

098000
type: LocalParameter
units: metaid_0000015
value: 0.5

097951
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000055

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

097722
type: LocalParameter
units: metaid_0000012
value: 1.0

097710
type: LocalParameter
units: metaid_0000016
value: 500.0

097698
type: LocalParameter
units: metaid_0000011
value: 0.0

097674
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000049

097662
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000071

097650
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000052

metaid_0000038
type: Parameter
constant: true
units: metaid_0000012
value: 0.636

metaid_0000024
type: Parameter
constant: true
units: metaid_0000012
value: 10.0

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

metaid_0000042
type: Parameter
constant: false
units: metaid_0000014
value: NaN

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

097470
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000083

097458
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000080

097482
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000070

097518
type: LocalParameter
units: metaid_0000012
value: 0.0167

097506
type: LocalParameter
units: metaid_0000016
value: 8.35

metaid_0000019
type: Parameter
constant: false
units: metaid_0000014
value: NaN

metaid_0000029
type: Parameter
constant: false
units: metaid_0000014
value: NaN

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

096771
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000067

096819
type: LocalParameter
units: metaid_0000015
value: 15.7

096783
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000069

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

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

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

096445
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

096433
type: SBMLUnit
exponent: -2.0
scale: 0
multipler: 1.0
kind: MOLE

096421
type: SBMLUnit
exponent: 6.0
scale: 0
multipler: 1.0
kind: METRE

096409
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1000000.0
kind: DIMENSIONLESS

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

096904
type: LocalParameter
units: metaid_0000012
value: 0.2

096891
type: LocalParameter
units: metaid_0000016
value: 1.0

096879
type: LocalParameter
units: metaid_0000011
value: 0.0

096855
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000063

096843
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000062

096831
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000060

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

097361
type: LocalParameter
units: metaid_0000012
value: 0.0

097349
type: LocalParameter
units: metaid_0000016
value: 6.0

097325
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000051

097313
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000050

097301
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000068

metaid_0000109
type: Reaction
modifier: 096940
is version of: http://identifiers.org/ec-code/3.1.4.17
kinetic law: 096952
product: 096928
name: PDE4
fast: false
reversible: true
reactant: 096916
is version of: GO:0004115

096964
type: LocalParameter
units: metaid_0000015
value: 1.3

096928
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000072

096916
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000083

metaid_0000105
type: Reaction
kinetic law: 096663
reversible: true
product: 096627
fast: false
reactant: 096615
product: 096639
is version of: GO:0004930
name: activate_Gs
product: 096651

096699
type: LocalParameter
units: metaid_0000013
value: 0.0

096687
type: LocalParameter
units: metaid_0000012
value: 0.025

096675
type: LocalParameter
units: metaid_0000011
value: 0.0

096627
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000063

096615
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000081

096639
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000068

096651
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000052

ORG:
  orgname: California Institute of Technology
n:
  given: Harish
  family: Dharuri