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Title: 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 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 PIP 3 at the plasma membrane and the soluble second messenger IP 3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above amore » threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cornell Univ., Ithaca, NY (United States)
  2. Cornell Univ., Ithaca, NY (United States)
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Report Number(s):
LA-UR-13-29273
Journal ID: ISSN 1664-3224
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Frontiers in Immunology
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 1664-3224
Publisher:
Frontiers Research Foundation
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science
OSTI Identifier:
1396113

Chylek, Lily A., Holowka, David A., Baird, Barbara A., and Hlavacek, William S.. An Interaction Library for the FcεRI Signaling Network. United States: N. p., Web. doi:10.3389/fimmu.2014.00172.
Chylek, Lily A., Holowka, David A., Baird, Barbara A., & Hlavacek, William S.. An Interaction Library for the FcεRI Signaling Network. United States. doi:10.3389/fimmu.2014.00172.
Chylek, Lily A., Holowka, David A., Baird, Barbara A., and Hlavacek, William S.. 2014. "An Interaction Library for the FcεRI Signaling Network". United States. doi:10.3389/fimmu.2014.00172. https://www.osti.gov/servlets/purl/1396113.
@article{osti_1396113,
title = {An Interaction Library for the FcεRI Signaling Network},
author = {Chylek, Lily A. and Holowka, David A. and Baird, Barbara A. and Hlavacek, William S.},
abstractNote = {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.},
doi = {10.3389/fimmu.2014.00172},
journal = {Frontiers in Immunology},
number = ,
volume = 5,
place = {United States},
year = {2014},
month = {4}
}