TABLE 2.
Critical parameters determining model output
Ligand binding
|
Receptor dimerization
|
Receptor phosphorylation
|
Trafficking
|
||||||
---|---|---|---|---|---|---|---|---|---|
Output variable | + | − | + | − | + | − | + | − | |
EGFR-EGFR | Total | 1 | 6 | 15,18 | 13,17 | 23,29 | 47 | ||
Surface | 15,18 | 13,17 | 23,29 | 43,47 | 41,45,49–52 | ||||
EGFR-HER2 | Total | 6 | 13,17 | 25,28,29 | 35,39,40 | ||||
Surface | 12,17 | 15 | 25,28,29 | 35 | 43,47 | 41,49–51 | |||
EGFR-HER3 | Total | 2 | 6,7,11 | 13 | 18 | 27,28,29 | 38 | 47 | 41,49 |
Surface | 7,11 | 13 | 18 | 27,28,29 | 43,47 | 41,49–52 | |||
HER2-HER3 | Total | 17 | 26,28,29 | 37 | |||||
Surface | 26,28,29 | 37 | 47 | 41,49 |
Parametric sensitivity analysis was performed by increasing each of the 54 model parameters (listed in Table 1) by 10%, one at a time, and studying the effect of this increase on the levels of activated dimers both at the whole-cell level and at the plasma membrane. Parameters that elicit a >2% change in the concentrations of the specific dimer species are listed. Parameter changes that result in an increase in the output, are listed in the plus (+) column; parameters whose increase results in a decrease in the output, are listed in the minus (−) column.