ArticleBlood2018
Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
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- Distinct Roles of apoE Receptor-2 Cytoplasmic Domain Splice Variants in Cardiometabolic Disease Modulation.Biomedicines · 2025Article
- Extracellular Vesicles Analysis as Possible Signatures of Antiphospholipid Syndrome Clinical Features.International journal of molecular sciences · 2025Article
- Impaired implantation as a major upstream pathway of preeclampsia: a narrative synthesis of mechanistic, epidemiological and biomarker evidence.Frontiers in reproductive health · 2025Review
- Mechanism of antiphospholipid antibody-mediated thrombosis in antiphospholipid syndrome.Frontiers in immunology · 2025Review
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- ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- The well-defined antiphospholipid syndrome induced by COVID-19: a rare case report and review of the literature.Thrombosis journal · 2024Review
- Berberine Targets PKM2 to Activate the t-PA-Induced Fibrinolytic System and Improves Thrombosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- STAT3-mediated up-regulation of DAB2 via SRC-YAP1 signaling axis promotes Helicobacter pylori-driven gastric tumorigenesis.Biomarker research · 2024Article
- Catastrophic Antiphospholipid Syndrome.International journal of molecular sciences · 2024Review
- Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome.Frontiers in immunology · 2024Review
- Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells.Biomedicines · 2023Article
- The pathogenesis of obstetric APS: a 2023 update.Clinical immunology (Orlando, Fla.) · 2023Review
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle.Nature communications · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of β2 glycoprotein I promotes thrombosis, and preclinical studies indicate that this is due to endothelial nitric oxide synthase (eNOS) antagonism via apolipoprotein E receptor 2 (apoER2)-dependent processes. How apoER2 molecularly links these events is unknown. Here, we show that, in endothelial cells, the apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of the heterotrimeric protein phosphatase 2A (PP2A). Disabled-2 (Dab2) recruitment to the apoER2 NPXY motif promotes the activating L309 methylation of the PP2A catalytic subunit by leucine methyl transferase-1. Concurrently, Src homology domain-containing transforming protein 1 (SHC1) recruits the PP2A scaffolding subunit to the proline-rich apoER2 C terminus along with 2 distinct regulatory PP2A subunits that mediate inhibitory dephosphorylation of Akt and eNOS. In mice, the coupling of these processes in endothelium is demonstrated to underlie aPL-invoked thrombosis. By elucidating these intricacies in the pathogenesis of APS-related thrombosis, numerous potential new therapeutic targets have been identified.
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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.