A mathematical model of insulin signaling in the apoptosis decision network

Bree Aldridge, Massachusetts Institute of Technology

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Insulin is a polypeptide hormone that promotes cell survival and regulates metabolism. Binding of insulin to the insulin receptor at the cell surface activates the receptor and initiates the insulin signaling netowrk. The insulin signaling network influences the cell survival/death decision process primarily through downstream effector proteins PKB (Akt) and SOS. We are developing a mathematical model of the insulin signaling network focusing on the pathways intersecting with the apoptosis decision network. The model consists of a system of ordinary differential equations in which elementary chemical reactions are modeled using mass-action kinetics. The model parameters and kinetic rate constants are gathered from literature and systematic quantitative experiments. Since cellular signaling pathways process as well as transduce signals, cell survival decisions must rest on key processing nodes in the signaling network. We hope to integrate this model with analogous models of the TNF (death ligand) and EGF (another survival factor) apoptosis signaling networks to elucidate the important processing nodes and computing mechanisms embedded in the decision network.

Abstract Author(s): Bree Aldridge, Birgit Schoeberl, Peter Sorger, Douglas Lauffenburger