TABLE 1.
Parameters used in the model
| Parameter No. | Parameter description | Value |
|---|---|---|
| Receptor-ligand binding rates | ||
| 1 | BR for EGF binding. | 2.38 × 10−6/nM/s |
| 2 | BR for NRG binding. | 2.38 × 10−6/nM/s |
| 3 | Multiplier for EGF binding rate in endosomes. | 0.135 |
| 4 | Multiplier for NRG binding rate in endosomes. | 0.135 |
| 5 | Multiplier for EGF binding to EGFR-HER3. | 0.5 |
| Ligand dissociation rates | ||
| 6 | BR for EGF dissociation. | 4 × 10−3/s |
| 7 | BR for NRG dissociation. | 4 × 10−3/s |
| 8 | Multiplier for EGF dissociation in endosomes. | 4.125 |
| 9 | Multiplier for NRG dissociation in endosomes. | 8.25 |
| 10 | Multiplier for NRG dissociation from HER2-HER3. | 0.1 |
| 11 | Multiplier for EGF dissociation from EGFR-HER3. | 1.5 |
| Receptor dimerization rates | ||
| 12 | Receptor dimerization rate. | 1 × 10−2/nM/s |
| Dimer dissociation rates | ||
| 13 | BR for EGFR homodimers. | 1 × 10−2/s |
| 14 | BR for HER2 homodimers. | 2.5 × 10−1/s |
| 15 | BR for EGFR-HER2. | 2 × 10−2/s |
| 16 | BR for HER3 homodimers. | 1 × 10−2/s |
| 17 | BR for HER2-HER3. | 2 × 10−2/s |
| 18 | BR for EGFR-HER3. | 1 × 10−2/s |
| 19 | Multiplier when phosphate is removed. | 2 |
| 20 | Multiplier when ligand is removed. | 5 |
| Receptor phosphorylation rates | ||
| 21 | BR for EGFR monomer. | 1 × 10−3/s |
| 22 | BR for HER2 monomer. | 2 × 10−4/s |
| 23 | BR for EGFR homodimers. | 1 × 10−2/s |
| 24 | BR for HER2 homodimers. | 8 × 10−3/s |
| 25 | BR. for EGFR-HER2. | 8 × 10−3/s |
| 26 | BR for HER2-HER3. | 8 × 10−3/s |
| 27 | BR for EGFR-HER3. | 8 × 10−3/s |
| 28 | Multiplier when a receptor is phosphorylated. | 3 |
| 29 | Multiplier when a receptor is bound. | 2 |
| Receptor dephosphorylation rates | ||
| 30 | BR for EGFR monomer. | 5 × 10−2/s |
| 31 | BR for HER2 monomer. | 5 × 10−2/s |
| 32 | BR for HER3 monomer. | 5 × 10−2/s |
| 33 | BR for EGFR homodimers. | 5 × 10−3/s |
| 34 | BR for HER2 homodimers. | 5 × 10−3/s |
| 35 | BR for EGFR-HER2. | 5 × 10−3/s |
| 36 | BR for HER3 homodimers. | 5 × 10−3/s |
| 37 | BR for HER2-HER3. | 5 × 10−3/s |
| 38 | BR for EGFR-HER3. | 5 × 10−3/s |
| 39 | Multiplier when phosphate is removed. | 2 |
| 40 | Multiplier when ligand is removed. | 4 |
| Vesicle trafficking rates | ||
| 41 | CP vesicle formation. | 2.1 × 10−1/s |
| 42 | SP vesicle formation. | 2.1 × 10−1/s |
| 43 | SP vesicle recycling. | 6.9 × 10−4/s |
| 44 | CP vesicle recycling. | 2.07 × 10−3/s |
| 45 | SP vesicle merging with LE. | 1.61 × 10−3/s |
| 46 | CP vesicle merging with LE. | 2.3 × 10−4/s |
| 47 | SP formation from LE. | 2.47 × 10−4/s |
| 48 | Lysosome formation from LE. | 1.3 × 10−5/s |
| Receptor incorporation factors | ||
| 49 | Factor for EE vesicles. | 7.94 × 10−4 |
| 50 | Multiplier for ligand-bound EGFR. | 15.5 |
| 51 | Multiplier for ligand-bound EGFR-HER2. | 5.4 |
| 52 | Multiplier for ligand-bound EGFR-HER3. | 5.4 |
| Degradation multipliers | ||
| 53 | Multiplier for single-ligand-bound EGFR. | 3 |
| 54 | Multiplier for doubly-bound EGFR homodimers. | 6 |
BR stands for the basal rate. Sources of these parameters and the manner in which these parameters are used to obtain rate constants for specific reactions are described in Appendix B.