ArticleJournal of immunology (Baltimore, Md. : 1950)2012
CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- INPP5D rs35349669 polymorphism with late-onset Alzheimer's disease: A replication study and meta-analysis.Oncotarget · 2016Pooled it
- Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.Nature genetics · 2013Pooled it
- Enhanced plasmacytoid dendritic cell antiviral responses after omalizumab.The Journal of allergy and clinical immunology · 2018Trial
- Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy.Clinical immunology (Orlando, Fla.) · 2014Trial
- Reprogramming of the hepatic ubiquitin‑immune axis: A unifying mechanism in liver disease progression (Review).Molecular medicine reports · 2026Review
- INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.bioRxiv : the preprint server for biology · 2025Article
- CD2AP at the junction of nephropathy and Alzheimer's disease.Molecular neurodegeneration · 2025Review
- SHIP-1 Differentially Regulates IgE-Induced IL-10 and Antiviral Responses in Human Monocytes.European journal of immunology · 2025Article
- Coupling of Alzheimer's Disease Genetic Risk Factors with Viral Susceptibility and Inflammation.Aging and disease · 2024Review
- Noncanonical function of folate through folate receptor 1 during neural tube formation.Nature communications · 2024Article
- INPP5D regulates inflammasome activation in human microglia.Nature communications · 2023Article
- SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis.The Journal of clinical investigation · 2023Article
- Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma.Frontiers in immunology · 2022Article
- Role of Microglia in Regulating Cholesterol and Tau Pathology in Alzheimer's Disease.Cellular and molecular neurobiology · 2021Review
- Type I Interferon Production of Plasmacytoid Dendritic Cells under Control.International journal of molecular sciences · 2021Review
- Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene.Neurobiology of aging · 2019Article
- cindr, the Drosophila Homolog of the CD2AP Alzheimer's Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis.Cell reports · 2019Article
- Tetrandrine enhances the ubiquitination and degradation of Syk through an AhR-c-src-c-Cbl pathway and consequently inhibits osteoclastogenesis and bone destruction in arthritis.Cell death & disease · 2019Article
- Leukocyte mono-immunoglobulin-like receptor 8 (LMIR8)/CLM-6 is an FcRγ-coupled receptor selectively expressed in mouse tissue plasmacytoid dendritic cells.Scientific reports · 2018Article
- Microglia in Alzheimer's disease.The Journal of cell biology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The human plasmacytoid dendritic cell (pDC) receptor BDCA2 forms a complex with the adaptor FcεR1γ to activate an ITAM-signaling cascade. BDCA2 receptor signaling negatively regulates the TLR7/9-mediated type 1 IFN responses in pDCs, which may play a key role in controlling self-DNA/RNA-induced autoimmunity. We report in this article that CD2-associated adaptor protein (CD2AP), which is highly expressed in human pDCs, positively regulates BDCA2/FcεR1γ receptor signaling. By immunoprecipitation and mass spectrometry analyses, we found that CD2AP bound to SHIP1. Knockdown of CD2AP or SHIP1 reduced the BDCA2/FcεR1γ-mediated ITAM signaling and blocked its inhibition of TLR9-mediated type 1 IFN production. Knockdown of CD2AP or SHIP1 also enhanced the ubiquitination and degradation of Syk and FcεR1γ that was mediated by the E3 ubiquitin ligase Cbl. This led us to discover that, upon BDCA2 cross-linking, the CD2AP/SHIP1 complex associated with Cbl and inhibited its E3 ubiquitin ligase activity. In human primary pDCs, cross-linking of the BDCA2/FcεR1γ complex induced the recruitment of the CD2AP/SHIP1/Cbl complex to the plasma membrane of pDCs, where it colocalized with the BDCA2/FcεR1γ complex. Therefore, CD2AP positively regulates BDCA2/FcεR1γ signaling by forming a complex with SHIP1 to inhibit the E3 ubiquitin ligase Cbl.
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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.