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Table 2 Parametric sensitivity analysis of the complete model for ERK1/2 activation

From: A rule-based model of insulin signalling pathway

Parameter Complete model wo_feedback P70S6K wo_feedback ERK1/2 Process
n_p70 −433.62 % - −553.98 % p70 mediated IRS1 phosphorylation at Ser
kcat33 158.53 % 159.60 % 207.34 % # Mek phosphorylation
kcat32 −157.47 % −158.57 % −202.56 % # Raf inactivation
k7 154.53 % 23.76 % 183.15 % # IRS-1 phosphorylation at Tyr
k_7 −154.50 % −23.96 % −183.05 % # IRS-1 dephosphorylation at Tyr
kcat28 152.95 % 65.18 % 189.32 % Ras activation
kcat29 −152.78 % −65.23 % −188.99 % # Raf activation
kcat30 150.90 % 62.38 % 185.97 % # Raf activation
k_7p 140.15 % 4.82 % 161.27 % # IRS-1 dephosphorylation at Ser
k15 −135.17 % - −155.79 % # IRS1 phosphorylation by P70S6K
kcat35 79.97 % 79.91 % 104.72 % Erk phosphorylation
kcat36 77.83 % 79.00 % 101.60 % Erk phosphorylation
k41 −34.20 % −16.98 % −43.11 % # IRS1-GS and IRS1-SHP2 complex disruption
kcat39 −23.10 % −25.16 % - GS inhibition
Kd_p70 20.02 % - 26.18 % p70 mediated IRS1 phosphorylation at Ser
Vmax 15.35 % 19.63 % 21.95 % PKC and p70 mediated IRS1 phosphorylation at Ser
k8 −13.39 % −9.24 % −17.15 % # IRS-1_PI3-K complex formation (PI3-K activation)
k_8 13.38 % 9.27 % 17.04 % # IRS-1_PI3-K complex dissociation
n 6.66 % 0.11 % 7.10 % PKC mediated IRS1 phosphorylation at Ser
k_21 −5.65 % - −6.50 % # TSC1-TSC2 T1462_phosphorylation_by_Akt_pT309
k9s 4.74 % 0.35 % 5.35 % # lipids PI(3,4,5)P3 formation
k9a −4.71 % −0.28 % −5.48 % # lipids PI(3,4,5)P3 formation
k7p −4.01 % −4.79 % −5.32 % # IRS-1 phosphorylation at Ser
k4p −2.62 % −10.56 % −4.01 % # Phosphorylated receptor internalization
k_39 2.62 % 2.10 % - GS inactivation
k_20 2.20 % - −0.21 % # p70S6K phosphorylation/dephosphorylation mediated by mTORC1_pS2448
kcat24 −1.71 % 87.60 % 17.49 % Src activation
kcat31 −1.70 % 87.58 % 17.35 % # Raf activation
alpha24 −1.60 % 87.59 % 17.48 % Src activation
k_4 0.77 % 2.59 % 0.88 % # Free receptor externalization
k_16 0.13 % −0.07 % −0.11 % # AMPK_T172 dephosphorylation mediated by IRS1_pY
Kd_pkc 0.11 % −0.02 % 0.00 % PKC mediated IRS1 phosphorylation at Ser
k12 0.10 % 0.04 % −0.03 % # PKC phosphorylation at Threonine
k6 0.08 % 0.12 % −0.01 % # Receptor unbinding and dephosphorylation (inside the cell)
k_2 0.05 % −0.11 % −0.17 % # Receptor binding 2nd insulin molecule
  1. Sensitivity coefficients are ranked accordingly to their absolute values and their corresponding values upon P70S6K-IRS1 and ERK1/2-GRB2/SOS negative feedback loop removal are also shown. Only coefficient greater than 0.1 % (absolute value) either in the original or modified models are reported. The column “Process” describes the biological process to which the parameter takes place