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. Author manuscript; available in PMC: 2010 Jan 25.
Published in final edited form as: Mol Biosyst. 2008 Sep 12;4(12):1151–1159. doi: 10.1039/b803806f

Table 1.

(a) Comparison of signaling and inhibition characteristics predicted by our network simulations for wildtype and mutant systems under different conditions; Del stands for the deletion mutant del L723–P729 ins S. Concentrations of Akt-(p) or ERK-(p) are used to indicate the downstream effects of receptor signaling. EC50 values are calculated as a measure of the degree to which signals downstream are inhibited by the ATP analogue, erlotinib. (b) Kinetic rate constants or species concentrations constituting the top three principal components for network hyper-sensitivity calculated through global sensitivity analysis: kf, turnover for phosphorylation; (•) denotes bound complex; the square brackets represent concentrations

(a) Wildtype L834R Del
ERK-(p) in nM for normal ErbB1 expression
−EGF/+EGF 0.2/5.0 1.0/1.0 8.0/8.0
Akt-(p) in nM for normal ErbB1 expression
−EGF/+EGF 1.0/15.0 13.0/13.0 20.0/20.0
ERK-(p) in nM for ErbB1 over-expression
−EGF/+EGF 3.0/3.0 5.0/5.0 1.0/1.0
Akt-(p) in nM for ErbB1 over-expression
−EGF/+EGF 20.0/20.0 22.0/22.0 19.0/19.0
Cellular EC50 in nM for inhibition of ERK-(p) and Akt-(p) for normal ErbB1 expression/ErbB1 over-expression
ERK-(p) 700/4000 100/1000 −/−
Akt-(p) 1200/500 000 300/50 000 −/−
(b) Rate and binding constants
kf: Y1068; kf: Y1173
Ki: inhibitor; KM: ATP•RTK
KM: GAB-1•ErbB1-(p)

Initial concentrations

[Raf•Ras•GTP]
[Pase3] phosphatase for ERK-(p)
[Pase4] phosphatase for Akt-(p)
[MEK-(p)]
[PI3K inactive]
[MEK•Raf active]
[ErbB1•Shc•Grb2•SOS• RasGTP]
[inhibitor]