BG_RTK

About this model

This is a bond-graph model of the metabolism of generic receptor tyrosine kinase (RTK) in the mammalian cell.

INPUTS:

Ligand (L) stimulus

OUTPUTS:

Change in molar amount of phosphorylated RTK K₂P_n

REACTIONS:

Re₁: the binding of L to one RTK (K₁)

Re₂: formation of complex of two RTK molecules which have dimerized, with ligand present (LK₁ K₂).

Re₃: autophosphorylation of RTKs in the dimer.

Re₄: binding of ubiquitin to resulting ligand-RTK complex

Re₅: Ubiquitin-tagged complex gets sorted for RTK to be recycled, and other constituents to be degraded.

Re₆: Ubiquitin-tagged complex gets sorted for RTK to be degraded by hydrolysis inside a lysosome.

Model status

The current CellML implementation runs in OpenCOR.

Model overview

The following model of RTK action is based on what is widely known in literature.

Bond-graph formulation of the generic RTK network. Because this model is generic, n would change depending on the chosen reaction. 'E' represents the RTK protein; 'tag' represents the protein that has been sorted for either recycling (reaction 5) or degradation (reaction 6) by ubiquitin U.

List of chemical species
Abbreviation	Name
K	Receptor tyrosine kinase (RTK)
L	Ligand
P_i	Phosphate
U	Ubiquitin

Parameter finding

A description of the process to find bond-graph parameters is shown in the folder parameter_finder, which relies on the:

stoichiometry of system
kinetic constants for forward/reverse reactions

If not already, all reactions are made reversible by assigning a small value to the reverse direction.

linear algebra script.

Here, this solve process is performed in Python.