ArticlePloS one2012
Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
- Kinetic frustration by limited bond availability controls the LAT protein condensation phase transition on membranes.Science advances · 2022Article
- PLCγ1 promotes phase separation of T cell signaling components.The Journal of cell biology · 2021Article
- Suppression of human T cell activation by derivatives of glycerol monolaurate.Scientific reports · 2021Article
- How the T cell signaling network processes information to discriminate between self and agonist ligands.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulation of Transmembrane Signaling by Phase Separation.Annual review of biophysics · 2019Review
- Understanding the Dynamics of T-Cell Activation in Health and Disease Through the Lens of Computational Modeling.JCO clinical cancer informatics · 2019Review
- The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters.The Journal of biological chemistry · 2015Review
- An Interaction Library for the FcεRI Signaling Network.Frontiers in immunology · 2014Review
- The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo.Science signaling · 2013Article
- Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling.BMC systems biology · 2012Article
- The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.Wiley interdisciplinary reviews. Systems biology and medicineReview
- Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The linker for activation of T cells (LAT), the linker for activation of B cells (LAB), and the linker for activation of X cells (LAX) form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate). We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.