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Modeling Activation and Desensitisation of G-Protein Coupled Receptors Provides Insight into Ligand Efficacy

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Model Status

This model is coded in terms of reaction elements. A number of values are missing. Unit consistency is poor and an attempt to rebuild the model using the differential equations defined in the paper was unsuccessful due to a lack of required information in the paper.

Model Structure

Signalling through G-protein coupled receptors is one of the most common and most important methods of transmitting information to the inside of cells. Many mathematical models have been published to describe this type of signal transduction, but the kinetic model described by Riccobene, Omann and Linderman (1999) is unique in that it includes the dynamics of G-protein activation and desensitisation, in addition to considering active and inactive receptor states (see the figure below). The model was used to predict how different ligands would affect the nature of the signal transduction response.

The complete original paper reference is cited below:

Modeling Activation and Desensitisation of G-Protein Coupled Receptors Provides Insight into Ligand Efficacy, Todd A. Riccobene, Geneva M. Omann and Jennifer J. Linderman, 1999 Journal of Theoretical Biology , 200, 207-222. (A PDF version of the article is available for Journal Members on the Journal of Theoretical Biology website.) PubMed ID: 10504286

The raw CellML description of the model can be downloaded in various formats as described in

A schematic diagram of Riccobene, Omann and Linderman's model of G-protein coupled receptor signalling. R is the inactive form of the receptor, R* is the active form of the receptor, Rds is the desensitised form of the receptor, L represents the ligand (in this case, N-formyl-norleucyl-leucyl-phenylalaninyl-nor-leucyl-tyrosyl-lysine-fluorescein, or CHO-NLFNTK-fl), G is the inactive G-protein, G* is the activated G-protein, and LR/LR*/LRds represents the ligand/receptor complex in its various forms.