ArticleFrontiers in immunology2015
GRB2 Nucleates T Cell Receptor-Mediated LAT Clusters That Control PLC-γ1 Activation and Cytokine Production.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Human Neutrophils Produce De Novo Thyroid Hormones Mediated by the Induction of the Oxidative Burst.Biomolecules · 2026Article
- Establishment and characterization of NKMS-1, a novel mouse NK cell line.Scientific reports · 2026Article
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- An Overview of Liquid-Liquid Phase Separation and Its Mechanisms in Sepsis.Journal of inflammation research · 2025Review
- GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production.Scientific reports · 2023Article
- Proteomic characterization of Omicron SARS-CoV-2 host response.Cell discovery · 2022Article
- Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function.Science signaling · 2021Article
- Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.Cell reports · 2021Article
- Suppression of human T cell activation by derivatives of glycerol monolaurate.Scientific reports · 2021Article
- The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions.Cellular signalling · 2020Article
- LRCH1 deficiency enhances LAT signalosome formation and CD8Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer.Journal for immunotherapy of cancer · 2020Article
- A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.Frontiers in immunology · 2018Article
- TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22.Scientific reports · 2017Article
- SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis.Nature cell biology · 2017Article
- Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production.Molecular immunology · 2017Article
- Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics.Scientific reports · 2016Article
- Phase separation of signaling molecules promotes T cell receptor signal transduction.Science (New York, N.Y.) · 2016Article
- Human Serum Albumin (HSA) Suppresses the Effects of Glycerol Monolaurate (GML) on Human T Cell Activation and Function.PloS one · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
GRB2 is a ubiquitously expressed adaptor protein required for signaling downstream of multiple receptors. To address the role of GRB2 in receptor-mediated signaling, the expression of GRB2 was suppressed in human CD4+ T cells and its role downstream of the T cell receptor (TCR) was examined. Interestingly, GRB2 deficient T cells had enhanced signaling from complexes containing the TCR. However, GRB2 deficient T cells had substantially reduced production of IL-2 and IFN-γ. This defect was attributed to diminished formation of linker for activation of T cells (LAT) signaling clusters, which resulted in reduced MAP kinase activation, calcium flux, and PLC-γ1 recruitment to LAT signaling clusters. Add back of wild-type GRB2, but not a novel N-terminal SH3 domain mutant, rescued LAT microcluster formation, calcium mobilization, and cytokine release, providing the first direct evidence that GRB2, and its ability to bind to SH3 domain ligands, is required for establishing LAT microclusters. Our data demonstrate that the ability of GRB2 to facilitate protein clusters is equally important in regulating TCR-mediated functions as its capacity to recruit effector proteins. This highlights that GRB2 regulates signaling downstream of adaptors and receptors by both recruiting effector proteins and regulating the formation of signaling complexes.
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