An Interaction Library for the FcεRI Signaling Network

Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are...

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Main Authors:	Chylek, Lily A., Holowka, David A., Baird, Barbara A., Hlavacek, William S.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995055/

id	pubmed-3995055
recordtype	oai_dc
spelling	pubmed-39950552014-04-29 An Interaction Library for the FcεRI Signaling Network Chylek, Lily A. Holowka, David A. Baird, Barbara A. Hlavacek, William S. Immunology Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein–protein and protein–lipid interactions. This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP3 at the plasma membrane and the soluble second messenger IP3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs. Frontiers Media S.A. 2014-04-15 /pmc/articles/PMC3995055/ /pubmed/24782869 http://dx.doi.org/10.3389/fimmu.2014.00172 Text en Copyright © 2014 Chylek, Holowka, Baird and Hlavacek. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chylek, Lily A. Holowka, David A. Baird, Barbara A. Hlavacek, William S.
spellingShingle	Chylek, Lily A. Holowka, David A. Baird, Barbara A. Hlavacek, William S. An Interaction Library for the FcεRI Signaling Network
author_facet	Chylek, Lily A. Holowka, David A. Baird, Barbara A. Hlavacek, William S.
author_sort	Chylek, Lily A.
title	An Interaction Library for the FcεRI Signaling Network
title_short	An Interaction Library for the FcεRI Signaling Network
title_full	An Interaction Library for the FcεRI Signaling Network
title_fullStr	An Interaction Library for the FcεRI Signaling Network
title_full_unstemmed	An Interaction Library for the FcεRI Signaling Network
title_sort	interaction library for the fcεri signaling network
description	Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein–protein and protein–lipid interactions. This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP3 at the plasma membrane and the soluble second messenger IP3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995055/
_version_	1612080684801720320

An Interaction Library for the FcεRI Signaling Network

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