ArticleThe EMBO journal2011
Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Weak SLP-76/PLC-γ1 interaction fine-tunes T cell receptor signal strength to optimize T cell responsiveness.Nature communications · 2026Article
- Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.Nature cancer · 2025Article
- Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.bioRxiv : the preprint server for biology · 2025Article
- Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T-Cell Adaptor Gads.European journal of immunology · 2025Article
- Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals.Zoological research · 2024Article
- Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.Frontiers in immunology · 2023Article
- Conformational switches that control the TEC kinase - PLCγ signaling axis.Journal of structural biology: X · 2022Review
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.The Journal of experimental medicine · 2021Article
- Three-dimensional localization microscopy in live flowing cells.Nature nanotechnology · 2020Article
- ERK Activation in CAR T Cells Is Amplified by CD28-Mediated Increase in CD3ζ Phosphorylation.iScience · 2020Article
- MgThe Journal of experimental medicine · 2019Article
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
- Molecular mechanisms underlying the evolution of the slp76 signalosome.Scientific reports · 2017Article
- Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation.Journal of molecular biology · 2015Article
- GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.Cellular signalling · 2015Article
- SLP-76 sterile α motif (SAM) and individual H5 α helix mediate oligomer formation for microclusters and T-cell activation.The Journal of biological chemistry · 2013Article
- Substrate recognition of PLCγ1 via a specific docking surface on Itk.Journal of molecular biology · 2013Article
- The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1.
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Registered trials
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.