Extracellular signal-regulated kinase (ERK)

Description of the model

According to the topology which is found as most likely by Xu et al (2010) a kinetic model is created. Literature data is used to estimate the parameter values and their error. We ended up in two different models. In one (non-modified model) only one reaction kinetic differs from Xu et al. (2010), the Sos-Activation (purple reaction) and is assumed be a binding process rather than enzyme catalysed. Furthermore we modelled the ERK-Activation as two step reaction, with the monophosphorylated ERK as intermediate. In the other one (modified model) further kinetics were changed in addition to these modifications (marked in red). So are the activation of EPAC and PKA by an agonist modelled as binding, C3G-Activation is modelled in two steps, first a binding to the receptor than a phosphorylation, and the Ras-Activation process is splitted in its elementary reactions, and their kinetics are therefore mass action. The differentiation in two different models is made to gain one model which is as close as possible to Xu et al. (2010) and another one, in which the reaction mechanism resemble the published one and therefore more measured parameter are available. The network topology is shown in the graph besides. Click on a reaction to have more information about it.

Reactions

BRaf-Inactivation BRaf-Activation(Rap1) BRaf-Activation(Ras) C3G-Activation C3G-Inactivation EGF-Binding EPAC and PKA-Activation(Cilostamide) EPAC-Activation(EPACA) EPAC-Inactivation ERK-Activation ERK-Inactivation MEK-Activation(BRaf) MEK-Activation(Raf1) MEK-Inactivation

PKA-Activation(PKAA) PKA-Inactivation Raf-1-Activation Raf-1-Removal Raf-1-Inactivation Rap1-Activation(EPAC) Rap1-Activation(C3G) Rap1-Inactivation(GAP) Ras-Activation Ras-Inactivation(GAP) Sos-Binding Sos-Removal (Sospp) Sos-Removal (Sosp)