ArticleThe Journal of clinical investigation2020
GRK2 suppresses lymphomagenesis by inhibiting the MALT1 proto-oncoprotein.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 17 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- GRK2-mediated phosphorylation and de-succinylation of PKM2 reduce macrophage glycolysis in rheumatoid arthritis.Acta pharmacologica Sinica · 2025Article
- A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.The Journal of clinical investigation · 2025Article
- G-protein coupled receptor kinase-2 regulates the migration of chronic lymphocytic leukaemia cells to sphingosine-1 phosphate in vitro and their trafficking in vivo.Scientific reports · 2025Article
- Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Advances in biological regulation · 2023Article
- The Paracaspase MALT1 in Cancer.Biomedicines · 2022Review
- The role of PI3K/AKT signaling pathway in gallbladder carcinoma.American journal of translational research · 2022Review
- Review
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- Role of GRK2 in Trophoblast Necroptosis and Spiral Artery Remodeling: Implications for Preeclampsia Pathogenesis.Frontiers in cell and developmental biology · 2021Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Antigen receptor-dependent (AgR-dependent) stimulation of the NF-κB transcription factor in lymphocytes is a required event during adaptive immune response, but dysregulated activation of this signaling pathway can lead to lymphoma. AgR stimulation promotes assembly of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to recruit components of the canonical NF-κB machinery and (b) a protease to cleave and inactivate specific substrates, including negative regulators of NF-κB. In multiple lymphoma subtypes, malignant B cells hijack AgR signaling pathways to promote their own growth and survival, and inhibiting MALT1 reduces the viability and growth of these tumors. As such, MALT1 has emerged as a potential pharmaceutical target. Here, we identified G protein-coupled receptor kinase 2 (GRK2) as a new MALT1-interacting protein. We demonstrated that GRK2 binds the death domain of MALT1 and inhibits MALT1 scaffolding and proteolytic activities. We found that lower GRK2 levels in activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) are associated with reduced survival, and that GRK2 knockdown enhances ABC-DLBCL tumor growth in vitro and in vivo. Together, our findings suggest that GRK2 can function as a tumor suppressor by inhibiting MALT1 and provide a roadmap for developing new strategies to inhibit MALT1-dependent lymphomagenesis.
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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.