Table 2.
Parameters of the model. Concentrations are tentatively expressed in µM. Because many are still unknown and probably vary from one cell type to another, the parameter values are selected in a semi-arbitrary manner so as to produce sustained oscillatory behaviour [7]. The main goal of the model is indeed to determine the types of dynamic behaviour associated with the regulatory structure of the Cdk network.
| symbol | definition | numerical values |
|---|---|---|
| Cdc20tot | total concentration of the protein Cdc20 | 5 µM |
| E2Ftot | total concentration of the transcription factor E2F | 3 µM |
| GF | growth factor | 1 µM |
| Kda | Michaelis constant for the degradation, activated by Cdc20, of cyclin A/Cdk2 | 0.1 µM |
| Kdb | Michaelis constant for the degradation, activated by Cdc20, of cyclin B/Cdk1 | 0.005 µM |
| Kdd | Michaelis constant for the degradation of cyclin D/Cdk4–6 | 0.1 µM |
| Kde | Michaelis constant for the degradation of cyclin E/Cdk2 | 0.1 µM |
| Kgf | Michaelis constant for synthesis of the cyclin D/Cdk4–6 complex induced by growth factor | 0.1 µM |
| K1cdc20 | Michaelis constant for Cdc20 activation through phosphorylation by cyclin B/Cdk1 | 1 µM |
| K2cdc20 | Michaelis constant for Cdc20 inactivation through dephosphorylation | 1 µM |
| K1e2f | Michaelis constant for E2F activation by cyclin D/Cdk4–6 and cyclin E/Cdk2 complexes | 0.01 µM |
| K2e2f | Michaelis constant for E2F inactivation by the cyclin A/Cdk2 complex | 0.01 µM |
| Vda | rate constant for the degradation of the cyclin A/Cdk2 complex by the protein Cdc20 | 0.245 h−1 |
| Vdb | rate constant for the degradation of the cyclin B/Cdk1 complex by the protein Cdc20 | 0.28 h−1 |
| Vdd | maximum degradation rate of cyclin D/Cdk4–6 complex | 0.245 µM h−1 |
| Vde | rate constant for the degradation of cyclin E/Cdk2 by cyclin A/Cdk2 | 0.35 h−1 |
| vsa | rate constant for synthesis of cyclin A/Cdk2 induced by the transcription factor E2F | 0.175 h−1 |
| vsb | rate constant for synthesis of cyclin B/Cdk1 induced by cyclin A/Cdk2 | 0.21 h−1 |
| vsd | rate constant for synthesis of cyclin D/Cdk4–6 induced by growth factor GF | 0.175 h−1 |
| vse | rate constant for synthesis of cyclin E/Cdk2 induced by the transcription factor E2F | 0.21 h−1 |
| V1cdc20 | rate constant for activation of Cdc20 through phosphorylation by cyclin B/Cdk1 | 0.21 h−1 |
| V2cdc20 | maximum rate constant for inactivation of Cdc20 through dephosphorylation | 0.35 µM h−1 |
| V1e2f | rate constant for activation of E2F by cyclin D/Cdk4–6 and cyclin E/Cdk2 complexes | 0.805 h−1 |
| V2e2f | rate constant for inactivation of E2F by the cyclin A/Cdk2 complex | 0.7 h−1 |