ArticleThe Journal of biological chemistry2011
A novel role for Bruton's tyrosine kinase in hepatocyte growth factor-mediated immunoregulation of dendritic cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- MET alterations are enriched in lung adenocarcinoma brain metastases, defining a distinct biologic subtype.The Journal of clinical investigation · 2026Article
- Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and meningioma.Medicine · 2025Article
- Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Lipid Mediators and Cytokines/Chemokines Display Differential Profiles in Severe versus Mild/Moderate COVID-19 Patients.International journal of molecular sciences · 2023Article
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.Molecular psychiatry · 2023Article
- Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect.Experimental hematology & oncology · 2022Review
- Article
- The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients.Nature communications · 2021Article
- Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies.Frontiers in oncology · 2021Review
- Targeting the NLRP3 Inflammasome via BTK.Frontiers in cell and developmental biology · 2021Review
- BTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects.Frontiers in immunology · 2021Review
- Runx proteins mediate protective immunity against Leishmania donovani infection by promoting CD40 expression on dendritic cells.PLoS pathogens · 2020Article
- Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells.British journal of cancer · 2020Article
- Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury.Stem cell research & therapy · 2019Article
- HGF/MET and the Immune System: Relevance for Cancer Immunotherapy.International journal of molecular sciences · 2018Review
- Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy.Nature reviews. Cancer · 2018Review
- The Impact of the Epithelial-Mesenchymal Transition Regulator Hepatocyte Growth Factor Receptor/Met on Skin Immunity by Modulating Langerhans Cell Migration.Frontiers in immunology · 2018Review
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The limited success of dendritic cell (DC)-based immunotherapy in multiple myeloma is partly due to hepatocyte growth factor (HGF)-induced DC dysfunction. From a therapeutic standpoint, it is important to understand the molecular events involved in inhibition of DC activation/maturation by HGF. Because Bruton's tyrosine kinase (Btk) negatively regulates maturation and immunostimulatory function of DCs, a role for Btk in HGF-induced inhibition of both murine and human DCs was investigated. We demonstrate that Btk is a novel proximal component of HGF-induced c-MET (HGF receptor) signaling. Following HGF treatment, Btk binds to c-MET and becomes activated. Btk activation in turn blocks the NF-κB pathway and subsequent DC activation via the c-Src-PI3K-AKT-mammalian target of rapamycin (mTOR) pathway. Notably, Btk activation is necessary for HGF-induced association of c-Src and PI3K with c-MET. Furthermore, we provide the first evidence that HGF inhibits DC activation by inducing autocrine interleukin (IL)-10 secretion, which requires activation of Btk. Blocking activation of Btk and its downstream the c-Src-PI3K-AKT-mTOR pathway prevents HGF-induced IL-10 secretion by DCs. In addition, neutralization of IL-10 secretion from DCs impaired the inhibitory effect of HGF on DCs. Thus, our study identifies a novel role for Btk in HGF-induced DC inhibition.
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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.