Can delays replace Phosphorylation – dephosphorylation cycles in signaling cascades?
by
Srividhya Jeyaraman
Indiana University School of Informatics and Biocomplexity Institute, Bloomington, IN, USA
Coauthors: M. S. Gopinathan (Indian Institute of Information Technology and Management, Kerala, India) Schnell, Santiago (Indiana University School of Informatics and Biocomplexity Institute)

Many biochemical pathways operate on signaling cascades consisting of a series of phosphorylation–dephosphorylation (PD) cycles. These cycles are coupled with several positive and negative regulations causing inherent delays during signal propagation. Modeling these complex signaling cascades with ordinary differential equations (ODE) often requires a large number of variables and parameters. Simplifying these ODE models with delays could prevent spending time on redundant mechanisms and focus on the key regulators of the dynamics.

Delay differential equation (DDE) models have been helpful in the description of inherent time delays and in the reduction of the number of variables [1]. However the consequences of model reduction via DDEs have not been fully explored. We have systematically examined the effect of delays in a complex network of PD cycles [2], which commonly occur in many biochemical pathways [3]. By introducing delays in the positive and negative regulatory interactions, we show that a delay model can indeed reduce the number of PD cycles and still describe the dynamics of the network effectively. In my presentation I will show the effects of the delays and how the results of this study can be extended to model complex biochemical pathways [4] .

References

1. Smolen, P., D.A. Baxter, and J.H. Byrne, Biophys. J., 2002. 83(5): p. 2349-2359.

2. Gonze, D. and A. Goldbeter, Journal of Theoretical Biology, 2001. 210(2): p. 167-186.

3. Srividhya, J., M.S. Gopinathan, and S. Schnell, Biophysical Chemistry, 2007. 125(2-3): p. 286-297.

4. Srividhya, J. and M.S. Gopinathan, Journal of Theoretical Biology, 2006. 241(3): p. 617-627.

Date received: May 15, 2008