ArticleThe Journal of experimental medicine2000
Bruton's tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04178798 (Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Early Stage CLL With High Risk of Early Disease Progression), which is not on this map. Cited by 116 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Early Stage CLL With High Risk of Early Disease Progression
Who cites it
116 citing papers in PubMed, 300 citations in OpenAlex.
- Safety, Tolerability, Pharmacokinetics, Target Occupancy, and Concentration-QT Analysis of the Novel BTK Inhibitor Evobrutinib in Healthy Volunteers.Clinical and translational science · 2020Trial
- Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.British journal of haematology · 2018Trial
- Trial
- Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.The New England journal of medicine · 2013Trial
- Targeting DNA Polymerase Epsilon Induces Tumor Clearance and Activates an NF-κB-Mediated Inflammatory Response in Triple-Negative Breast Cancer.Cancer research · 2026Article
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Targeting DNA Polymerase Epsilon Leads to Tumor Clearance and Activation of an NF-κB-mediated inflammatory response in Triple Negative Breast Cancer.bioRxiv : the preprint server for biology · 2025Article
- Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotypes and phenotypes in chronic lymphocytic leukemia.Genome research · 2025Article
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.Annals of hematology · 2025Review
- Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis.Journal of medicinal chemistry · 2024Article
- Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes.Antibodies (Basel, Switzerland) · 2024Review
- Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotype and phenotype in chronic lymphocytic leukemia.bioRxiv : the preprint server for biology · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- The function of serine/threonine-specific protein kinases in B cells.Frontiers in immunology · 2024Review
- Readministration of high-dose adeno-associated virus gene therapy vectors enabled by ImmTOR nanoparticles combined with B cell-targeted agents.PNAS nexus · 2023Article
- Identification of immune infiltration-related biomarkers in carotid atherosclerotic plaques.Scientific reports · 2023Article
- Influence of Bruton's Tyrosine Kinase (BTK) on Epithelial-Mesenchymal Transition (EMT) Processes and Cancer Stem Cell (CSC) Enrichment in Head and Neck Squamous Cell Carcinoma (HNSCC).International journal of molecular sciences · 2023Article
- Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation.Molecules (Basel, Switzerland) · 2023Article
- Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.Cell reports · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-kappaB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-kappaB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IkappaB kinase (IKK), which normally targets the NF-kappaB inhibitor IkappaBalpha for degradation. Taken together, these findings indicate that BTK couples IKK and NF-kappaB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid.
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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.