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Table 3 FOXO parameters for synthesis, degradation, transport and PTMs

From: Computational modelling of the regulation of Insulin signalling by oxidative stress

Process

2orate constant (#min-1)

Enzyme

Enz #

1orate const (min-1)

PTM modifying rate

Rate MF

Reference

Synthesis (NULL → FOXO)

0.0055

E2F1

300

5.5

  

[45] Figure 1

Cytoplasm → nuclear transport

-

-

-

0.1/0.55 = 0.182

  

[3], [46]

     

Akt-Phos Pa

0.1

[46]

     

IKK-Phos Pd

0.5

[47] Figure 1

     

JNK-Phos Pe

10

[44]

Nuclear → cytoplasm transport

-

-

-

0.1 × 0.55 = 0.055

  

[3], [46]

     

Akt-Phos Pa

10

[46]

     

IKK-phos Pd

10

[47]

     

JNK-Phos Pe

0.1

[44]

Nuclear → DNAbound transport

-

-

-

0.25

  

[48]

     

Akt-Phos Pa

0.5

[49] Figure 6B

DNAbound → Nuclear transport

-

-

-

0.25 × 0.5 = 0.125

  

[48]

basal phosphorylation

5 × 10-5

      

basal dephosphorylation

1 × 10-6

      

akt_phos_

factor

6

      

ikk phos_factor

3

      

jnk phos_factor

2

      

FOXO → FOXO_Pa

akt phos_factor × basal phosphorylation

Akt

(104)

0.5

  

[50] Figure 1C

FOXO_Pa → FOXO

basal dephosphorylation

PP2A

5 × 105

0.5

   

FOXO → FOXO_Pd

ikk phos_factor × basal phosphorylation

IKK

(104)

0.5

  

[47]

FOXO_Pd → FOXO

basal dephosphorylation

PP2A

5 × 105

0.5

   

FOXO → FOXO_Pe

jnk phos_factor × basal phosphorylation

JNK

(104)

0.5

  

[44]

FOXO_Pe → FOXO

basal dephosphorylation

PP2A

5 × 105

0.5

   

FOXO → FOXO_pUb

1 × 10-6

SCF/MDM2

103

10-3

  

[45] Figure 1; also [51]

     

Akt (Pa)

3

[45] Figure 1

     

IKK (Pd)

22

[47] Figure 5F

Degradation (FOXO_pUb → NULL)

1 × 10-4

Proteasome

103

0.1

  

[45] Figure 1

  1. Kinetic parameters of the FOXO module of the model. Where a second-order rate constant is given and the Enzyme is time-varying, the Enz # and first order rate constant columns show typical values when the process is activated. The PTM modifying rate refers to the way modifiable species are implemented in this system: if the PTM is present, then the basal rate for the process (in the 1o rate column) is multiplied by the entry in the Rate MF (Multiplicative Factor) column.