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Table 1 Table summarizes the top 10 most sensitive system parameters for the global sensitivity analysis concerning integrated β-casein (left), transcription time delay (middle) and time-dependent switch (right). For each output parameter, some of the hypothesized mechanisms are highlighted. For example, for transcription time delay the mRNA and STAT transport rates are in bold

From: Time-dependent antagonist-agonist switching in receptor tyrosine kinase-mediated signaling

Casein (JAK-independent in bold)

Delay (Transport Reactions in Bold)

Ratio (Heterodimerization reactions in bold)

Parameter

Name

Parameter

Name

Parameter

Name

n_transc

Transcription Hill Coefficient

kR45

mRNA Nuclear Export Casein

kfR41

HER4 Heterodimerization

V_transc

Transcription Half-Maximum rate

kR25

Translation

kR39

STATc Phosphorylation JAK independent

kR46

mRNA degradation rate

kR20

Nuclear STAT dimer dephosphorylation

kfR36

IFNR (HER4 s80) Formation

kR20

Nuclear STAT dimer dephosphorylation

kR46

mRNA degradation rate

kfR01

HER4 JAK Binding

kR39

STATc Phosphorylation JAK independent

kR15

STAT Dimer Nuclear Translocation

kR37

IFNR (HER4 s80) Activation

kfR41

HER4 Heterodimerization

kR24

mRNA Nuclear Export

kfR42

HER4 Heterodimerization Constitutive

kfR36

IFNR (HER4 s80) Formation

kfR29

STATc SOCS HER4 JAK SHP Binding

kfR43

HER4 Heterodimer Ligand Binding

kR37

IFNR (HER4 s80) Activation

SOCS_Binding_Rate

SOCS Mediated negative feedback

kR06

STATc Phosphorylation JAK Dependent

kfR19

Nuclear STAT Dimer PPN Binding

kfR19

Nuclear STAT Dimer PPN Binding

kR25

Translation

K_transc

Transcription Equilibrium Coefficient

kfR43

HER4 Heterodimer Ligand Binding

SOCS_Binding_Rate

SOCS Mediated negative feedback