Physiology

Reaction Diagram

reactionDiagram

Cross-References

Annotations

Reactions

Reactions
Name
Structure
Kinetics
Depiction
SHC_p_cytoSHC_cyto SHC dephosphorylation cyto MassAction
MEK_cytoMEK_active_cyto MEk activation cyto HMMIrreversible
MAPK_active_cytoMAPK_active_N_nucleus nuclear transport nuclear Membrane MassAction
EGFR_cyto_mem+EGF_extraEGFR_active receptor ligand binding cyto_mem MassAction
Ras_GDP_cyto_memRas_GTP_cyto_mem Ras activation by Sos cyto_mem HMMIrreversible
MAPK_active_cytoMAPK_cyto MAPK inactivation cyto HMMIrreversible
MAPK_cytoMAPK_active_cyto MAPK activation cyto HMMIrreversible
PP2A_inactivePP2A_cyto r0 cyto MassAction
Raf_active_cytoRaf_cyto Raf inactivation cyto HMMIrreversible
Ras_GTP_cyto_memRas_GDP_cyto_mem Ras GAP cyto_mem HMMIrreversible
Raf_cytoRaf_active_cyto Raf activation cyto_mem HMMIrreversible
MEK_active_cytoMEK_cyto MEK inactivation cyto HMMIrreversible
EGFR_GAP_Grb2+Sos_cytoEGFR_GAP_GRb2_Sos Sos binding cyto_mem MassAction
SHC_cytoSHC_p_cyto Shc phosphorylation cyto_mem HMMIrreversible
GAP+EGFR_dimerEGFR_GAP GAP binding cyto_mem MassAction
SHC_p_cyto+EGFR_GAP_GRb2_SosEGFR_Sos_Grb2_Shc_cyto_mem Shc binding EGFR cyto_mem MassAction
EGFR_activeEGFR_dimer dimerization cyto_mem MassAction
EGFR_GAP+Grb2_cytoEGFR_GAP_Grb2 GRb2 binding cyto_mem MassAction

Structures

Name
Type
Electrical
cyto_mem Membrane cyto(+)   extra(-)
nuclear Membrane Membrane nucleus(+)   cyto(-)
extra Compartment (+)   (-)
nucleus Compartment (+)   (-)
cyto Compartment (+)   (-)

Species

Name
Structure
BioNetGen Definition
Depiction
MAPK_active_N_nucleus nucleus nucleus
Raf_active_cyto cyto cyto
ATP cyto cyto
EGFR_active cyto_mem cyto_mem
GAP cyto cyto
EGFR_GAP cyto_mem cyto_mem
MEK_cyto cyto cyto
MAPK_active_cyto cyto cyto
EGFR_cyto_mem cyto_mem cyto_mem
EGFR_dimer cyto_mem cyto_mem
Ras_GDP_cyto_mem cyto_mem cyto_mem
Ras_GAP_cyto cyto cyto
MEK_active_cyto cyto cyto
MAPK_cyto cyto cyto
EGF_extra extra extra
Sos_cyto cyto cyto
SHC_p_cyto cyto cyto
Ras_GTP_cyto_mem cyto_mem cyto_mem
SHC_cyto cyto cyto
EGFR_GAP_GRb2_Sos cyto_mem cyto_mem
Raf_cyto cyto cyto
EGFR_Sos_Grb2_Shc_cyto_mem cyto_mem cyto_mem
Grb2_cyto cyto cyto
PP2A_cyto cyto cyto
EGFR_GAP_Grb2 cyto_mem cyto_mem
PP2A_inactive cyto cyto

Molecules

Name
BioNetGen Definition
DEPICTION

Observables

Name
Structure
Count
BNGL Definition
Sequence Type
DEPICTION

Applications

Name
Properties Math Type
Annotation
compartmental Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental
ellipse_0999 receptor activation only Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_0999) (copied from compartmental)
circle Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
ellipse_099_nucleus1_1 Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
ellipse_099_nucleus3_1 Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_099_nucleus1_1) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
ellipse_099_nucleus5_1 Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_099_nucleus3_1) (copied from ellipse_099_nucleus1_1) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
spatially varying diffusion and receptor number Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
circle fine mesh Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from circle) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)
ellipse fine mesh Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Spatial (2D) (copied from ellipse_099_nucleus5_1) (copied from ellipse_099_nucleus3_1) (copied from ellipse_099_nucleus1_1) (copied from ellipse_0999 receptor activation only) (copied from ellipse_0999) (copied from compartmental)

Specifications (Species) - compartmental go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 0.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 0.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 0.0 [um2/s] cyto
ATP 5000.0 [uM] 0.0 [um2/s] cyto
GAP 0.1 [uM] 0.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 0.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 0.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 0.0 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 0.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 0.0 [um2/s] cyto
Sos_cyto 0.1 [uM] 0.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 0.0 [um2/s] cyto
SHC_cyto 0.5 [uM] 0.0 [um2/s] cyto
Raf_cyto 0.2 [uM] 0.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 0.0 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.1 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.0 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.0 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - compartmental go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - compartmental go to Specifications

Name
End Time
Output Options
Simulation0 3600.0

OutputTimeStep 10.0

Simulation13 1.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial107399510

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - ellipse_0999 receptor activation only go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 3.7 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.112 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - ellipse_0999 receptor activation only go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - ellipse_0999 receptor activation only go to Specifications

Name
End Time
Output Options
Simulation12 60.0

OutputTimeStep 10.0

Copy of Simulation12 1 3600.0

OutputTimeStep 10.0

Copy of Copy of Simulation12 1 7200.0

OutputTimeStep 10.0

varying diffusion of EGFR 3600.0

OutputTimeStep 10.0

varying receptor density 3600.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry Mathieu ellipse 0999 with nucleus ratio 6

(Origin: -30.0, -3.0, 0.0; Extent: 60.0, 6.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical nucleus 11.673486088379706 [um2] nucleus
Volume Analytical cell 158.12602291325695 [um2] cyto
Volume Analytical ECM 190.20049099836334 [um2] extra
Surface ECM_cell_membrane ECM | cell 109.6318051248791 [um] cyto_mem
Surface cell_nucleus_membrane cell | nucleus 37.823588052652646 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - circle go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - circle go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - circle go to Specifications

Name
End Time
Output Options
Simulation1 480.0

OutputTimeStep 10.0

Simulation2 7200.0

OutputTimeStep 10.0

Copy of Simulation1 60.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry circle with nucleus ratio 6 feb 2009

(Origin: -8.0, -8.0, 0.0; Extent: 16.0, 16.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical nucleus 12.313600000000001 [um2] nucleus
Volume Analytical cyto 156.97920000000002 [um2] cyto
Volume Analytical ecm 86.7072 [um2] extra
Surface cyto_ecm_membrane cyto | ecm 46.21278101811295 [um] cyto_mem
Surface cyto_nucleus_membrane cyto | nucleus 12.415157207294083 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - ellipse_099_nucleus1_1 go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - ellipse_099_nucleus1_1 go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - ellipse_099_nucleus1_1 go to Specifications

Name
End Time
Output Options
Simulation5 15000.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry ellipse sep 08 0999 with cyt-n 2:1

(Origin: -23.5, -1.25, 0.0; Extent: 47.0, 2.5, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical subdomain0 37.682249999999996 [um2] nucleus
Volume Analytical Cell 37.29449999999999 [um2] cyto
Volume Analytical ECM 42.52324999999999 [um2] extra
Surface Cell_ECM_membrane Cell | ECM 93.46482136095845 [um] cyto_mem
Surface Cell_subdomain0_membrane Cell | subdomain0 65.35262936922854 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - ellipse_099_nucleus3_1 go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - ellipse_099_nucleus3_1 go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - ellipse_099_nucleus3_1 go to Specifications

Name
End Time
Output Options
Simulation3 15000.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry ellipse sep 08 0999 with cyt-n 4:1

(Origin: -23.5, -1.25, 0.0; Extent: 47.0, 2.5, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical subdomain0 18.858749999999997 [um2] nucleus
Volume Analytical Cell 56.117999999999995 [um2] cyto
Volume Analytical ECM 42.52324999999999 [um2] extra
Surface Cell_ECM_membrane Cell | ECM 93.46482136095845 [um] cyto_mem
Surface Cell_subdomain0_membrane Cell | subdomain0 46.33232970167217 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - ellipse_099_nucleus5_1 go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - ellipse_099_nucleus5_1 go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - ellipse_099_nucleus5_1 go to Specifications

Name
End Time
Output Options
Simulation4 15000.0

OutputTimeStep 10.0

Copy of Simulation4 60.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry ellipse sep 08 0999 with cyt-n 6:1

(Origin: -23.5, -1.25, 0.0; Extent: 47.0, 2.5, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical subdomain0 12.560749999999999 [um2] nucleus
Volume Analytical Cell 62.41599999999999 [um2] cyto
Volume Analytical ECM 42.52324999999999 [um2] extra
Surface Cell_ECM_membrane Cell | ECM 93.46482136095845 [um] cyto_mem
Surface Cell_subdomain0_membrane Cell | subdomain0 38.29432490973859 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - spatially varying diffusion and receptor number go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 3.7 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem (213.0 * (1.0 + (0.018 * abs(x)))) [uM] (0.112 * (1.0 + (0.018 * abs(x)))) [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] (0.08 * (1.0 + (0.03 * abs(x)))) [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - spatially varying diffusion and receptor number go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - spatially varying diffusion and receptor number go to Specifications

Name
End Time
Output Options
Simulation6 60.0

OutputTimeStep 10.0

Simulation7 3600.0

OutputTimeStep 10.0

Simulation8 7200.0

OutputTimeStep 10.0

Simulation9 3600.0

OutputTimeStep 10.0

Simulation10 3600.0

OutputTimeStep 10.0

Copy of Simulation6 480.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry Mathieu ellipse 0999 with nucleus ratio 6

(Origin: -30.0, -3.0, 0.0; Extent: 60.0, 6.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical nucleus 12.308944744072456 [um2] nucleus
Volume Analytical cell 156.20637020453853 [um2] cyto
Volume Analytical ECM 191.48468505138905 [um2] extra
Surface ECM_cell_membrane ECM | cell 108.81799234890245 [um] cyto_mem
Surface cell_nucleus_membrane cell | nucleus 36.43730612082122 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - circle fine mesh go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - circle fine mesh go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - circle fine mesh go to Specifications

Name
End Time
Output Options
Simulation11 60.0

OutputTimeStep 10.0

Simulation14 7200.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry circle with nucleus ratio 6 feb 2009

(Origin: -8.0, -8.0, 0.0; Extent: 16.0, 16.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical nucleus 12.313600000000001 [um2] nucleus
Volume Analytical cyto 156.97920000000002 [um2] cyto
Volume Analytical ecm 86.7072 [um2] extra
Surface cyto_ecm_membrane cyto | ecm 46.21278101811295 [um] cyto_mem
Surface cyto_nucleus_membrane cyto | nucleus 12.415157207294083 [um] nuclear Membrane

Events

Name Variable Rate Expression

Specifications (Species) - ellipse fine mesh go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
EGF_extra 1.0 [uM] 1.0 [um2/s] extra
MAPK_active_N_nucleus 0.0 [uM] 7.0 [um2/s] nucleus
Raf_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
ATP 5000.0 [uM] 10.0 [um2/s] cyto
GAP 0.1 [uM] 10.0 [um2/s] cyto
MEK_cyto 0.18 [uM] 6.0 [um2/s] cyto
MAPK_active_cyto 0.0 [uM] 7.0 [um2/s] cyto
Ras_GAP_cyto 0.002 [uM] 4.14 [um2/s] cyto
MEK_active_cyto 0.0 [uM] 6.0 [um2/s] cyto
MAPK_cyto 0.36 [uM] 7.0 [um2/s] cyto
Sos_cyto 1.0 [uM] 10.0 [um2/s] cyto
SHC_p_cyto 0.0 [uM] 6.4 [um2/s] cyto
SHC_cyto 1.0 [uM] 6.4 [um2/s] cyto
Raf_cyto 0.2 [uM] 7.0 [um2/s] cyto
Grb2_cyto 1.0 [uM] 8.5 [um2/s] cyto
PP2A_cyto 0.0 [uM] 0.0 [um2/s] cyto
PP2A_inactive 0.05 [uM] 0.0 [um2/s] cyto
EGFR_active 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_GAP 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_cyto_mem 400.0 [uM] 0.04 [um2/s] cyto_mem
EGFR_dimer 0.0 [uM] 0.08 [um2/s] cyto_mem
Ras_GDP_cyto_mem 500.0 [uM] 0.16 [um2/s] cyto_mem
Ras_GTP_cyto_mem 0.0 [uM] 0.16 [um2/s] cyto_mem
EGFR_GAP_GRb2_Sos 0.0 [uM] 0.0 [um2/s] cyto_mem
EGFR_Sos_Grb2_Shc_cyto_mem 0.0 [uM] 0.08 [um2/s] cyto_mem
EGFR_GAP_Grb2 0.0 [uM] 0.0 [um2/s] cyto_mem

Specifications (Reaction) - ellipse fine mesh go to Simulations

Name
Enabled?
SHC dephosphorylation included
MEk activation included
nuclear transport included
receptor ligand binding included
Ras activation by Sos included
MAPK inactivation included
MAPK activation included
r0 included
Raf inactivation included
Ras GAP included
Raf activation included
MEK inactivation included
Sos binding included
Shc phosphorylation included
GAP binding included
Shc binding EGFR included
dimerization included
GRb2 binding included

Simulations - ellipse fine mesh go to Specifications

Name
End Time
Output Options
Simulation15 60.0

OutputTimeStep 10.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry ellipse sep 08 0999 with cyt-n 6:1

(Origin: -23.5, -1.25, 0.0; Extent: 47.0, 2.5, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Volume Analytical subdomain0 12.40975935828877 [um2] nucleus
Volume Analytical Cell 62.52005347593583 [um2] cyto
Volume Analytical ECM 42.5701871657754 [um2] extra
Surface Cell_ECM_membrane Cell | ECM 93.03794179617861 [um] cyto_mem
Surface Cell_subdomain0_membrane Cell | subdomain0 37.60040211638436 [um] nuclear Membrane

Events

Name Variable Rate Expression

Global Parameters

Name
Expression
n 1200.0[molecules.um-2.uM-1]