TCR signalisation

Summary:

Klamt et al. proposed in [1] a Boolean model of the TCR signalling pathway. The model encompasses 40 regulatory components. In this version of the model an auto-regulation has been added on each input.

Analysis

This model has been studied in [2], using novel algorithms for the analysis of feedback circuits and the determination of stable states. The stable state analysis shows seven stable states, listed bellow. Each stable state corresponds to a different input combination, except "111". Indeed, the systems shows an oscilatory behaviour under full activation.

CD45	CD8	TCRlig	TCRbind	PAGCsk	Fyn	TCRphos	Ikb
0	*	0	0	1	0	0	1
0	*	1	1	0	0	0	1
1	0	0	0	1	0	0	1
1	0	1	1	0	1	1	1
1	1	0	0	1	0	0	1

Table 1. 7 stable states of the model. A "*" means "all possible expression levels (i.e. 0 or 1). The expression level of all other variables is 0.

The feedback circuit analysis shows nine circuits, besides the three auto-activation on the inputs. Only one of these circuits is functional: (ZAP70, cCbl). This negative circuit is functional in presence of LCK and TCRphos which can only be maintained in presence of the three inputs. This circuit drives the oscillatory behaviour observed under full activation.

References

Klamt S, Saez-Rodriguez J, Lindquist JA, Simeoni L, Gilles ED. 2006. A methodology for the structural and functional analysis of signaling and regulatory networks. BMC Bioinformatics. 7(1):56.
Naldi A, Thieffry D, Chaouiya C. 2007. Decision Diagrams for the Representation and Analysis of Logical Models of Genetic Networks. Computational Methods in Systems Biology. 4695:233-247.

Curation

Submitter:

Claudine Chaouiya

Supporting Paper :

A methodology for the structural and functional analysis of signaling and regulatory networks

Model metadata

Model file(s):

TCRsig40.zginml

Description:

Regulatory Model