Gray2016 - The Akt switch model

  public model
Model Identifier
BIOMD0000000854
Short description 
This is a simple, linear, four-compartment ordinary differential equation (ODE) model Akt activation that tracks both the phosphorylation state and the physical location (cytosol, plasma membrane) of Akt.
Format
SBML (L2V4)
Related Publication
  • The Akt switch model: Is location sufficient?
  • Gray CW, Coster ACF
  • Journal of theoretical biology , 6/ 2016 , Volume 398 , pages: 103-111 , PubMed ID: 26992575
  • School of Mathematics and Statistics, UNSW, Sydney, Australia. Electronic address: catheryn.gray@unsw.edu.au.
  • Akt/PKB is a biochemical regulator that functions as an important cross-talk node between several signalling pathways in the mammalian cell. In particular, Akt is a key mediator of glucose transport in response to insulin. The phosphorylation (activation) of only a small percentage of the Akt pool of insulin-sensitive cells results in maximal translocation of glucose transporter 4 (GLUT4) to the plasma membrane (PM). This enables the diffusion of glucose into the cell. The dysregulation of Akt signalling is associated with the development of diabetes, cancer and cardiovascular disease. Akt is synthesised in the cytoplasm in the inactive state. Under the influence of insulin, it moves to the PM, where it is phosphorylated to form pAkt. Although phosphorylation occurs only at the PM, pAkt is found in many cellular locations, including the PM, the cytoplasm, and the nucleus. Indeed, the spatial distribution of pAkt within the cell appears to be an important determinant of downstream regulation. Here we present a simple, linear, four-compartment ordinary differential equation (ODE) model of Akt activation that tracks both the biochemical state and the physical location of Akt. This model embodies the main features of the activation of this important cross-talk node and is consistent with the experimental data. In particular, it allows different downstream signalling motifs without invoking separate feedback pathways. Moreover, the model is computationally tractable, readily analysed, and elucidates some of the apparent anomalies in insulin signalling via Akt.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer

Metadata information

hasTaxon (1 statement)
Taxonomy Mus musculus

hasProperty (2 statements)
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology protein kinase B signaling

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

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Name Description Size Actions

Model files
Gray2016.xml SBML L2V4 Representation of Gray2016 - The Akt switch model 36.44 KB Preview | Download

Additional files
Gray2016.cps COPASI file of Gray2016 - The Akt switch model 59.13 KB Preview | Download
Gray2016.sedml SED-ML file of Gray2016 - The Akt switch model 2.85 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Nov 13, 2019 11:35:33 AM
  • Last Modified: Nov 13, 2019 11:35:33 AM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Nov 13, 2019 11:35:33 AM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000854
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Pc

AKT kinase ; phosphoprotein ; cytosol 		0.0 nmol
Pp

AKT kinase ; phosphoprotein ; plasma membrane 		0.0 nmol
Ap

AKT kinase ; plasma membrane 		0.05 nmol
Ac

AKT kinase ; cytosol 		0.95 nmol
Reactions
Reactions Rate Parameters
Pc => Ac compartment*koff*Pc koff = 0.35
Pp => Ap compartment*koff*Pp koff = 0.35
Ap => Pp compartment*beta1*koff*Ap beta1 = 2.2; koff = 0.35
Pc => Pp compartment*alpha1*kin*Pc alpha1 = 0.014; kin = 0.55
Ac => Ap compartment*alpha1*kin*Ac alpha1 = 0.014; kin = 0.55
Pp => Pc compartment*kin*Pp kin = 0.55
Curator's comment:
(added: 13 Nov 2019, 11:35:17, updated: 13 Nov 2019, 11:35:17)
Reproduced plot of Figure 7(b) in the original publication, simulated with alpha values corresponding to 1 nM insulin. Model simulated and plot produced using COPASI 4.24 (Build 197).