ArticlePloS one2012
Src kinase and Syk activation initiate PI3K signaling by a chimeric latent membrane protein 1 in Epstein-Barr virus (EBV)+ B cell lymphomas.
Article in PloS one, 2012. 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, 35 citations in OpenAlex.
- Visomitin as a differentiation-inducing therapeutic agent through SYK inhibition in AML.Frontiers in pharmacology · 2026Article
- Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.Cell reports. Medicine · 2024Article
- FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.Cellular and molecular life sciences : CMLS · 2024Article
- A PNPLA3-Deficient iPSC-Derived Hepatocyte Screen Identifies Pathways to Potentially Reduce Steatosis in Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2024Article
- Role of Fyn in hematological malignancies.Journal of cancer research and clinical oncology · 2023Review
- CD11c regulates neutrophil maturation.Blood advances · 2023Article
- FYN: emerging biological roles and potential therapeutic targets in cancer.Journal of translational medicine · 2023Review
- Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments.International journal of molecular sciences · 2022Review
- Article
- Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells.BMC complementary medicine and therapies · 2020Article
- Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Epstein-Barr Virus Latent Membrane Protein 1 Regulates Host B Cell MicroRNA-155 and Its Target FOXO3aFrontiers in microbiology · 2019Article
- Inhibitor of apoptosis proteins (IAPs) mediate collagen type XI alpha 1-driven cisplatin resistance in ovarian cancer.Oncogene · 2018Article
- Inhibition of ovarian tumor cell invasiveness by targeting SYK in the tyrosine kinase signaling pathway.Oncogene · 2018Article
- A novel orally available Syk/Src/Jak2 inhibitor, SKLB-850, showed potent anti-tumor activities in B cell lymphoma (BCL) models.Oncotarget · 2017Article
- LMP1 signaling pathway activates IRF4 in latent EBV infection and a positive circuit between PI3K and Src is required.Oncogene · 2017Article
- 1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties.Molecules (Basel, Switzerland) · 2016Article
- Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis.The Journal of biological chemistry · 2015Article
- Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes.PLoS neglected tropical diseases · 2014Article
- The interplay between Epstein-Barr virus and B lymphocytes: implications for infection, immunity, and disease.Immunologic research · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The B lymphotrophic γ-herpesvirus EBV is associated with a variety of lymphoid- and epithelial-derived malignancies, including B cell lymphomas in immunocompromised and immunosuppressed individuals. The primary oncogene of EBV, latent membrane protein 1 (LMP1), activates the PI3K/Akt pathway to induce the autocrine growth factor, IL-10, in EBV-infected B cells, but the mechanisms underlying PI3K activation remain incompletely understood. Using small molecule inhibition and siRNA strategies in human B cell lines expressing a chimeric, signaling-inducible LMP1 protein, nerve growth factor receptor (NGFR)-LMP1, we show that NGFR-LMP1 utilizes Syk to activate PI3K/Akt signaling and induce IL-10 production. NGFR-LMP1 signaling induces phosphorylation of BLNK, a marker of Syk activation. Whereas Src kinases are often required for Syk activation, we show here that PI3K/Akt activation and autocrine IL-10 production by NGFR-LMP1 involves the Src family kinase Fyn. Finally, we demonstrate that NGFR-LMP1 induces phosphorylation of c-Cbl in a Syk- and Fyn-dependent fashion. Our results indicate that the EBV protein LMP1, which lacks the canonical ITAM required for Syk activation, can nevertheless activate Syk, and the Src kinase Fyn, resulting in downstream c-Cbl and PI3K/Akt activation. Fyn, Syk, and PI3K/Akt antagonists thus may present potential new therapeutic strategies that target the oncogene LMP1 for treatment of EBV+ B cell lymphomas.
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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.