ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Biochemical and genetic evidence for a SAP-PKC-theta interaction contributing to IL-4 regulation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- The Differentiation and Maintenance of SARS-CoV-2-Specific Follicular Helper T Cells.Frontiers in cellular and infection microbiology · 2022Review
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1.International journal of molecular sciences · 2021Review
- NK cell recognition of hematopoietic cells by SLAM-SAP families.Cellular & molecular immunology · 2019Review
- Compartmentalization of dendritic cell and T-cell interactions in the lymph node: Anatomy of T-cell fate decisions.Immunological reviews · 2019Review
- Insights Into the Molecular Mechanisms of T Follicular Helper-Mediated Immunity and Pathology.Frontiers in immunology · 2018Review
- Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.The Journal of experimental medicine · 2017Article
- Review
- Responses to Microbial Challenges by SLAMF Receptors.Frontiers in immunology · 2016Review
- CRISPR-Mediated Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ Triple Gene Disruption Reveals NKT Cell Defects but Not T Follicular Helper Cell Defects.PloS one · 2016Article
- CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports Positive Signaling Roles in NKT Cell Development.PloS one · 2016Article
- Diacylglycerol Kinases: Shaping Diacylglycerol and Phosphatidic Acid Gradients to Control Cell Polarity.Frontiers in cell and developmental biology · 2016Review
- Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015Review
- The Novel PKCθ from Benchtop to Clinic.Journal of immunology research · 2015Review
- T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.European journal of immunology · 2014Article
- Emerging concepts on T follicular helper cell dynamics in HIV infection.Trends in immunology · 2014Review
- Article
- Modulation of SAP dependent T:B cell interactions as a strategy to improve vaccination.Current opinion in virology · 2013Review
- Molecular mechanisms of T cell co-stimulation and co-inhibition.Nature reviews. Immunology · 2013Review
- Role of diacylglycerol kinases in T cell development and function.Critical reviews in immunology · 2013Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Signaling lymphocytic activation molecule-associated protein (SAP), an adaptor molecule that recruits Fyn to the signaling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors, is mutated in X-linked lymphoproliferative disease. CD4(+) T cells from SAP-deficient mice have defective TCR-induced and follicular Th cell IL-4 production and impaired T cell-mediated help for germinal center formation; however, the downstream intermediates contributing to these defects remain unclear. We previously found that SAP-deficient CD4(+) T cells exhibit decreased protein kinase C (PKC)-theta recruitment upon TCR stimulation. We demonstrate in this paper using GST pulldowns and coimmunoprecipitation studies that SAP constitutively associates with PKC- in T cells. SAP-PKC-theta interactions required R78 of SAP, a residue previously implicated in Fyn recruitment, yet SAP's interactions with PKC-theta occurred independent of phosphotyrosine binding and Fyn. Overexpression of SAP in T cells increased and sustained PKC-theta recruitment to the immune synapse and elevated IL-4 production in response to TCR plus SLAM-mediated stimulation. Moreover, PKC-theta, like SAP, was required for SLAM-mediated increases in IL-4 production, and, conversely, membrane-targeted PKC-theta mutants rescued IL-4 expression in SAP(-/-) CD4(+) T cells, providing genetic evidence that PKC-theta is a critical component of SLAM/SAP-mediated pathways that influence TCR-driven IL-4 production.
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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.