ArticleThe EMBO journal2001
PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- A Systematic Review on the Role of the Stria Vascularis in Menière's Disease Pathogenesis.Journal of the Association for Research in Otolaryngology : JARO · 2025Pooled it
- Penetrant PKCβ mutation in ATLL displays a mixed gain-of-function.The Biochemical journal · 2025Article
- Phosphorylation-Inducing Molecules for Regulating Dynamic Cellular Processes.Journal of the American Chemical Society · 2025Article
- Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation.Thrombosis and haemostasis · 2025Article
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- Identification of Potential Diagnostic Biomarkers of Carotid Atherosclerosis in Obese Populations.Journal of inflammation research · 2025Article
- In BTK, phosphorylated Y223 in the SH3 domain mirrors catalytic activity, but does not influence biological function.Blood advances · 2024Article
- Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR.Science signaling · 2024Article
- The function of serine/threonine-specific protein kinases in B cells.Frontiers in immunology · 2024Review
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
- Targeted protein posttranslational modifications by chemically induced proximity for cancer therapy.The Journal of biological chemistry · 2023Review
- Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus.Diabetes research and clinical practice · 2023Article
- PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling.Cancers · 2022Article
- Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.Toxics · 2022Article
- Synthetic Reprogramming of Kinases Expands Cellular Activities of Proteins.Angewandte Chemie (International ed. in English) · 2022Article
- Calcium-dependent signalling in B-cell lymphomas.Oncogene · 2021Review
- Profiling transcriptomic changes and signaling pathways in atopic dermatitis by integrative analyses on multiple databases.Molecular genetics and genomics : MGG · 2021Article
- Genetic and Non-Genetic Mechanisms of Resistance to BCR Signaling Inhibitors in B Cell Malignancies.Frontiers in oncology · 2020Article
- A novel transgenic mouse strain expressing PKCβII demonstrates expansion of B1 and marginal zone B cell populations.Scientific reports · 2020Article
- Feedback Regulation of Syk by Protein Kinase C in Human Platelets.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in Bruton's tyrosine kinase (Btk) result in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. While targeted disruption of the protein kinase C-beta (PKCbeta) gene in mice results in an immunodeficiency similar to xid, the overall tyrosine phosphorylation of Btk is significantly enhanced in PKCbeta-deficient B cells. We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. These findings provide a novel mechanism whereby reversible translocation of Btk/Tec kinases regulates the threshold for immunoreceptor signaling and thereby modulates lymphocyte activation.
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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.