ArticleCell death & disease2018
Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification.Cell death & disease · 2026Article
- Functional sQTLs regulating PTK2B exon 31 splicing uncover an RNA-dependent modulation of its kinase activity and cellular phenotype.Cell communication and signaling : CCS · 2026Article
- CD95 ligand drives abdominal aortic aneurysm progression through Caspase-8-mediated GSDMD-dependent endothelial pyroptosis: modulation by SRC kinase.Apoptosis : an international journal on programmed cell death · 2026Article
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- The E3 ligase c-Cbl modulates microglial phenotypes and contributes to Parkinson's disease pathology.Cell death discovery · 2025Article
- NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance.Communications biology · 2022Article
- Review
- Prototheca spp. induce an inflammatory response via mtROS-mediated activation of NF-κB and NLRP3 inflammasome pathways in bovine mammary epithelial cell cultures.Veterinary research · 2021Article
- The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity.Cells · 2021Review
- Gatekeepers of the Gut: The Roles of Proteasomes at the Gastrointestinal Barrier.Biomolecules · 2021Review
- An update on the regulatory mechanisms of NLRP3 inflammasome activation.Cellular & molecular immunology · 2021Review
- Inflammasome activation controlled by the interplay between post-translational modifications: emerging drug target opportunities.Cell communication and signaling : CCS · 2021Review
- VEGF-Independent Activation of Müller Cells by the Vitreous from Proliferative Diabetic Retinopathy Patients.International journal of molecular sciences · 2021Article
- Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation.Frontiers in immunology · 2021Article
- Leukotriene BProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cbl Negatively Regulates NLRP3 Inflammasome Activation through GLUT1-Dependent Glycolysis Inhibition.International journal of molecular sciences · 2020Article
- Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma.Molecular & cellular proteomics : MCP · 2020Article
- Gain-of-function mutations in a member of the Src family kinases cause autoinflammatory bone disease in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice.Nutrients · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the NLRP3 inflammasome is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Pyk2 is essential for NLRP3 inflammasome activation. Here we show that the Src-family kinases (SFKs)-Cbl axis plays a pivotal role in suppressing NLRP3 inflammasome activation in response to stimulation by nigericin or ATP, as assessed using gene knockout and gene knockdown cells, dominant active/negative mutants, and pharmacological inhibition. We reveal that the phosphorylation of Cbl is regulated by SFKs, and that phosphorylation of Cbl at Tyr371 suppresses NLRP3 inflammasome activation. Mechanistically, Cbl decreases the level of phosphorylated Pyk2 (p-Pyk2) through ubiquitination-mediated proteasomal degradation and reduces mitochondrial ROS (mtROS) production by contributing to the maintenance of mitochondrial size. The lower levels of p-Pyk2 and mtROS dampen NLRP3 inflammasome activation. In vivo, inhibition of Cbl with an analgesic drug, hydrocotarnine, increases inflammasome-mediated IL-18 secretion in the colon, and protects mice from dextran sulphate sodium-induced colitis. Together, our novel findings provide new insights into the role of the SFK-Cbl axis in suppressing NLRP3 inflammasome activation and identify a novel clinical utility of hydrocortanine for disease treatment.
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