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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