Modeling the early signaling events mediated by FcεRI

Goldstein, Byron; Faeder, James R.; Hlavacek, William S.; Blinov, Michael L.; Redondo, Antonio; Wofsy, Carla

doi:10.1016/s0161-5890(02)00066-4

Cited by 52 publications

(88 citation statements)

References 25 publications

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“…Computational and theoretical models have been applied to complement experimental studies to help unravel the interplay of complex-competing effects in various aspects of T-cell signaling (Altan-Bonnet and Germain 2005;Cemerski et al 2007;Chakraborty and Das 2010;Das et al 2009;Goldstein et al 2002;Lee et al 2003). This is advantageous because computational models can keep track of the outcomes of different mechanistic hypotheses for each signaling component and determine whether each hypothesis yields results consistent with experimental observations.…”

Section: Computational Approaches To Understand Synapse Functionmentioning

confidence: 99%

Understanding the Structure and Function of the Immunological Synapse

Dustin¹,

Chakraborty²,

Shaw³

2010

Cold Spring Harbor Perspectives in Biology

211

202

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Section: Computational Approaches To Understand Synapse Functionmentioning

confidence: 99%

Understanding the Structure and Function of the Immunological Synapse

Dustin¹,

Chakraborty²,

Shaw³

2010

Cold Spring Harbor Perspectives in Biology

211

202

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“…In the case of the signaling cascade initiated by the aggregation of Fc⑀RI, the high affinity receptor for IgE, detailed molecular level models have been used to characterize the role of Lyn kinase in the initiation and regulation of Fc⑀RI tyrosine phosphorylation (3,4). We have recently extended these earlier models to investigate the separate roles of the receptor subunits and the kinases Lyn and Syk in the phosphorylation and activation of Syk (5). Here we provide a detailed description of the model and improved estimates of parameters based on direct experimental measurements and comparison of model predictions with both new and previously reported experimental data.…”

mentioning

confidence: 99%

Investigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model

Faeder¹,

Hlavacek²,

Reischl

et al. 2003

The Journal of Immunology

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163

346

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Aggregation of FcεRI on mast cells and basophils leads to autophosphorylation and increased activity of the cytosolic protein tyrosine kinase Syk. We investigated the roles of the Src kinase Lyn, the immunoreceptor tyrosine-based activation motifs (ITAMs) on the β and γ subunits of FcεRI, and Syk itself in the activation of Syk. Our approach was to build a detailed mathematical model of reactions involving FcεRI, Lyn, Syk, and a bivalent ligand that aggregates FcεRI. We applied the model to experiments in which covalently cross-linked IgE dimers stimulate rat basophilic leukemia 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 β- and γ-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 β ITAM acts to amplify signaling in experimental systems where its role has been investigated, there are conditions under which the β ITAM will act as an inhibitor.

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“…[364][365][366][367] Through model simulations, it has been shown how changing the ligand concentration, and consequently the concentration of while the ability of the BCR to interact with both conventional as well as nonconventional EC ligands is eliminated.…”

Section: School Model Of Fcεri Receptor Signalingmentioning

confidence: 99%

The SCHOOL of nature: I. Transmembrane signaling

2010

Self/Nonself

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Cell surface receptors are integral membrane proteins and, as such, consist of three basic domains: extracellular (EC) ligandbinding domains, transmembrane (TM) domains and cytoplasmic (CYTO) signaling (or effector) domains. Upon recognition and binding of a specific ligand, cell surface receptors transmit this information into the interior of the cell, activating intracellular signaling pathways and resulting in a cellular response such as proliferation, differentiation, apoptosis, degranulation, the secretion of preformed and newly formed mediators,

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Modeling the early signaling events mediated by FcεRI

Cited by 52 publications

References 25 publications

Understanding the Structure and Function of the Immunological Synapse

Understanding the Structure and Function of the Immunological Synapse

Investigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model

The SCHOOL of nature: I. Transmembrane signaling

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