Kinetic equations are usually written in terms of concentrations (not of mole numbers), since the reaction rates are functions of concentrations. If the same compound participates in reactions taking place in different compartments with different volumes, the effective concentration of that compound will be different depending on the volume of the corresponding compartment. Step 1 (EGF binding to EGFR) could be considered as taking place in the extracellular compartment with a given initial concentration of EGF. The concentration of EGFR in the extracellular compartment would then be calculated as the number of the receptors on the cell surface divided by the (average) volume of incubation medium per cell (V m). In step 2, association and dissociation of the receptor monomers occurs in the cell membrane. All other steps are considered as taking place in the cytosolic compartment. Therefore, the same mole number of EGFR would give rise to three EGFR concentrations (representing the different compartments). However, for computational purposes, it is more convenient to deal only with a single concentration of EGFR related to the cytoplasmic water volume (V cw) of the cell. This requires rescaling the rate constants of steps 1 and 2. For the purpose of this rescaling, the EGF concentration in the model was also related to the cytoplasmic water volume; i.e. [EGF] in the experimental medium was multiplied by the ratio Vm/V cw (see TableII). Typically, there were 107cells/ml in our experiments (see “Cell Preparation and Incubation Conditions”); therefore, Vm = 10−7 ml. Assuming the diameter of a hepatocyte of 20 μm and a cytoplasmic water volume of about 70% of total intracellular volume, Vm/Vcw = 33.3. [taken from Kholodenko 1999; http://www.jbc.org/content/274/42/30169.long] Per = 0 [without Inhibitor Pertuzumab] Per = 300000 [with Inhibitor Pertuzumab] - Stuart Moodie $\frac{\mathrm{ERKP}+\mathrm{ERKPP}}{\mathrm{tERKP\_max}}$ $\frac{\mathrm{Akt\_PI\_PP}+\mathrm{Akt\_PI\_P}+\mathrm{Akt\_PI\_PP\_PP2A}+\mathrm{Akt\_PI\_P\_PP2A}}{\mathrm{pAkt\_max}}$ $\frac{\mathrm{PTENP}}{7.6}$ $\mathrm{PTENP}+\mathrm{PTEN}+\mathrm{PTENP\_PTEN}+\mathrm{PTEN\_PTEN}+\mathrm{PTEN\_PIP3}+\mathrm{PTEN\_PI}$ $\frac{\mathrm{E23HP}+\mathrm{E23HP\_PI3K}+\mathrm{E23HP\_PI3Ka}+\mathrm{E23HP\_Shc}+\mathrm{E23HP\_ShcP}+\mathrm{E23HP\_ShGS}}{\mathrm{tE3P\_max}}$ $\mathrm{k1}(\mathrm{E3}\mathrm{HRG}-\mathrm{Kd\_1}\mathrm{E3H})$ $\frac{\mathrm{V10}\mathrm{ShcP}}{\mathrm{K10}+\mathrm{ShcP}}$ $\frac{\mathrm{k11}\mathrm{RasGDP}\mathrm{ShGS}}{\mathrm{K11}+\mathrm{RasGDP}}$ $\frac{\mathrm{V12}\mathrm{RasGTP}}{\mathrm{K12}+\mathrm{RasGTP}}$ $\frac{\mathrm{k13}\mathrm{Raf}\mathrm{RasGTP}}{\mathrm{K13}+\mathrm{Raf}}$ $\frac{\mathrm{k14}\mathrm{Rafa}(\mathrm{Akt\_PI\_PP}+\mathrm{E\_raf})}{\mathrm{Rafa}+\mathrm{K14}}$ $\frac{\mathrm{k15}\mathrm{MEK}\mathrm{Rafa}}{\mathrm{K15}+\mathrm{MEK}}$ $\mathrm{k16}\mathrm{MEKP}\mathrm{PP2A}$ $\mathrm{k16\_kat}\mathrm{MEKP\_PP2A}$ $\mathrm{k18}\mathrm{MEK\_PP2A}$ $\frac{\mathrm{k15}\mathrm{MEKP}\mathrm{Rafa}}{\mathrm{K15}+\mathrm{MEKP}}$ $\mathrm{k16}(\mathrm{PP2A}\mathrm{MEKPP}-\mathrm{Kd\_16}\mathrm{MEKPP\_PP2A})$ $\mathrm{k16\_kat}\mathrm{MEKPP\_PP2A}$ $\mathrm{k22}\mathrm{MEKP\_PP2A}$ $\frac{\mathrm{k23}\mathrm{ERK}\mathrm{MEKPP}}{\mathrm{K23}+\mathrm{ERK}}$ $\mathrm{k2}(\mathrm{E3H}\mathrm{E2}-\mathrm{Kd\_2}\mathrm{E23H})$ $\frac{\mathrm{V24}\mathrm{ERKP}}{\mathrm{K24}+\mathrm{ERKP}}$ $\frac{\mathrm{k23}\mathrm{ERKP}\mathrm{MEKPP}}{\mathrm{K23}+\mathrm{ERKP}}$ $\frac{\mathrm{V24}\mathrm{ERKPP}}{\mathrm{K24}+\mathrm{ERKPP}}$ $\mathrm{k27}(\mathrm{E23HP}\mathrm{PI3K}-\mathrm{Kd\_27}\mathrm{E23HP\_PI3K})$ $\mathrm{k28}(\mathrm{E23HP\_PI3K}-\mathrm{k\_28}\mathrm{E23HP\_PI3Ka})$ $\mathrm{k29}\mathrm{E23HP\_PI3Ka}-\mathrm{k\_29}\mathrm{E23HP}\mathrm{PI3Ka}$ $\mathrm{V30}\mathrm{PI3Ka}$ $\mathrm{k31}(\mathrm{PI2}\mathrm{PI3Ka}-\mathrm{K\_d31}\mathrm{PI3Ka\_PI})$ $\mathrm{k32}(\mathrm{PIP3}\mathrm{PTEN}-\mathrm{Kd\_32}\mathrm{PTEN\_PIP3})$ $\mathrm{k33}\mathrm{PTEN\_PIP3}$ $\mathrm{k34}\mathrm{PTEN\_PI}$ $\frac{\mathrm{V35}\mathrm{PTEN}}{\mathrm{K35}+\mathrm{PTEN}}$ $\mathrm{k36}(\mathrm{PTEN}\mathrm{PTENP}-\mathrm{Kd\_36}\mathrm{PTENP\_PTEN})$ $\mathrm{k37}\mathrm{PTENP\_PTEN}$ $\mathrm{k38}\mathrm{PTEN\_PTEN}$ $\mathrm{k39}(\mathrm{PIP3}\mathrm{Akt}-\mathrm{Kd\_39}\mathrm{Akt\_PIP3})$ $\mathrm{k3}(\mathrm{E23H}-\mathrm{Kd\_3}\mathrm{E23HP})$ $\frac{\mathrm{V40}\mathrm{Akt\_PIP3}}{\mathrm{K40}+\mathrm{Akt\_PIP3}}$ $\mathrm{k41}\mathrm{Akt\_PI\_P}\mathrm{PP2A}$ $\mathrm{k42}\mathrm{Akt\_PI\_P\_PP2A}$ $\mathrm{k43}\mathrm{Akt\_PIP3\_PP2A}$ $\frac{\mathrm{V40}\mathrm{Akt\_PI\_P}}{\mathrm{K40}+\mathrm{Akt\_PI\_P}}$ $\mathrm{k41}(\mathrm{Akt\_PI\_PP}\mathrm{PP2A}-\mathrm{Kd\_41}\mathrm{Akt\_PI\_PP\_PP2A})$ $\mathrm{k42}\mathrm{Akt\_PI\_PP\_PP2A}$ $\mathrm{k47}\mathrm{Akt\_PI\_P\_PP2A}$ $\mathrm{k48}\mathrm{E23HP}$ $\mathrm{k49}(\mathrm{Per}\mathrm{E2}-\mathrm{Kd\_49}\mathrm{E2\_Per})$ $\mathrm{k50}\mathrm{E2\_Per}-\mathrm{k\_50}\mathrm{E2Per}$ $\mathrm{k51}\mathrm{E3H}$ $\mathrm{k2}(\mathrm{E3H\_C}\mathrm{E2}-\mathrm{Kd\_2}\mathrm{E23H})$ $\mathrm{k53}\mathrm{E23H}$ $\frac{\mathrm{V4}\mathrm{E23HP}}{\mathrm{K4}+\mathrm{E23HP}}$ $\mathrm{k3}(\mathrm{E23H\_C}-\mathrm{Kd\_3}\mathrm{E23HP})$ $\mathrm{k55}\mathrm{PI3Ka\_PI}$ $\mathrm{k56}\mathrm{PI3Ka\_PIP3}$ $\mathrm{k57}(\mathrm{PTEN}\mathrm{bpV}-\mathrm{Kd\_57}\mathrm{PTEN\_bpV})$ $\mathrm{k58}(\mathrm{PI3K}\mathrm{LY}-\mathrm{Kd\_58}\mathrm{PI3K\_LY})$ $\mathrm{k5}(\mathrm{E23HP}\mathrm{Shc}-\mathrm{Kd\_5}\mathrm{E23HP\_Shc})$ $\mathrm{k6}\mathrm{E23HP\_Shc}-\mathrm{k\_6}\mathrm{E23HP\_ShcP}$ $\mathrm{k7}(\mathrm{E23HP\_ShcP}\mathrm{GS}-\mathrm{Kd\_7}\mathrm{E23HP\_ShGS})$ $\mathrm{k8}(\mathrm{E23HP\_ShGS}-\mathrm{Kd\_8}\mathrm{E23HP}\mathrm{ShGS})$ $\mathrm{k9}(\mathrm{ShGS}-\mathrm{k\_9}\mathrm{ShcP}\mathrm{GS})$