Modeling the early signaling events mediated by FcεRI

We present a detailed mathematical model of the phosphorylation and dephosphorylation events that occur upon ligand-induced receptor aggregation, for a transfectant expressing FcεRI, Lyn, Syk and endogenous phosphatases that dephosphorylate exposed phosphotyrosines on FcεRI and Syk. Through model simulations we show how changing the ligand concentration, and consequently the concentration of receptor aggregates, can change the nature of a cellular response as well as its amplitude. We illustrate the value of the model in analyzing experimental data by using it to show that the intrinsic rate of dephosphorylation of the FcεRI immunoreceptor tyrosine-based activation motif (ITAM) in rat basophilic leukemia (RBL) cells is much faster than the observed rate, provided that all of the cytosolic Syk is available to receptors. Published by Elsevier Science Ltd.