• B. Goldstein, J. R. Faeder, W. S. Hlavacek, M. L. Blinov, A. Redondo, and C. Wofsy.

  "Modeling the early signaling events mediated by aggregation of FceRI."

  Mol Immunol 2002 38(16-18), 1213-1219. (PUBMED abstract | Full text pdf)
  

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• J.R. Faeder, W.S. Hlavacek, I.Reischl, M.L. Blinov, H. Metzger, A. Redondo, C. Wofsy and B. Goldstein

  Investigation of Early Events in FceRI-Mediated Signaling using a Detailed Mathematical Model

  Abstract: Aggregation of FceRI on mast cells and basophils leads to autophosphorylation and increased activity of the cytosolic protein tyrosine kinase Syk. We investigate the roles of the Src kinase Lyn, the ITAMs (immunoreceptor tyrosine-based activation motifs) on the beta and gamma subunits of FceRI, and Syk itself in the activation of Syk. Our approach is to build a detailed mathematical model of reactions involving FceRI, Lyn, Syk, and a bivalent ligand that aggregates FceRI. We apply the model to experiments in which covalently cross-linked IgE dimers stimulate rat basophilic leukemia (RBL) cells. The model makes it possible to test the consistency of mechanistic assumptions with data that, alone, provide limited mechanistic insight. For example, the model helps sort out mechanisms that jointly control dephosphorylation of receptor subunits. In addition, interpreted in the context of the model, experimentally observed differences between the beta and gamma chains with respect to levels of phosphorylation and rates of dephosphorylation indicate that most cellular Syk, but only a small fraction of Lyn, is available to interact with receptors. We also show that although the beta ITAM acts to amplify signaling in experimental systems where its role has been investigated, there are conditions under which the beta ITAM will acts as an inhibitor
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