ArticleNature immunology2011
STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development.
Article in Nature immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 127 citations in OpenAlex.
- Restoring B cell intrinsic tolerance to lupus autoimmunity: a rational strategy for lupus treatment.Frontiers in immunology · 2026Review
- The Role of LAIR1 as a Regulatory Receptor of Antitumor Immune Cell Responses and Tumor Cell Growth and Expansion.Biomolecules · 2025Review
- H3K27 Trimethylation-Mediated Downregulation of miR-216a-3p in Sensory Neurons Regulates Neuropathic Pain Behaviors via Targeting STIM1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- PKCδ Protects against Lupus Autoimmunity.Biomedicines · 2024Review
- B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia.Frontiers in oncology · 2024Review
- Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer.Science advances · 2023Article
- Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.Toxicology and applied pharmacology · 2023Article
- RasGRP1 promotes the acute inflammatory response and restricts inflammation-associated cancer cell growth.Nature communications · 2022Article
- B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.Immunological reviews · 2022Review
- Article
- Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines.Nature communications · 2022Article
- Cardiomyocyte stromal interaction molecule 1 is a key regulator of CaPhysiological reports · 2022Article
- Article
- Impaired respiratory burst contributes to infections in PKCδ-deficient patients.The Journal of experimental medicine · 2021Article
- Striatal transcriptome changes linked to drug-induced repetitive behaviors.The European journal of neuroscience · 2021Article
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- CRAC Channels and Calcium Signaling in T Cell-Mediated Immunity.Trends in immunology · 2020Review
- To B, or not to B: Is calcium the answer?Cell calcium · 2020Article
- BCALM (AC099524.1) Is a Human B Lymphocyte-Specific Long Noncoding RNA That Modulates B Cell Receptor-Mediated Calcium Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Clonal deletion of autoreactive B cells is crucial for the prevention of autoimmunity, but the signaling mechanisms that regulate this checkpoint remain undefined. Here we characterize a previously unrecognized Ca(2+)-driven pathway for activation of the kinase Erk, which was proapoptotic and biochemically distinct from Erk activation induced by diacylglycerol (DAG). This pathway required protein kinase C-δ (PKC-δ) and the guanine nucleotide-exchange factor RasGRP and depended on the concentration of the Ca(2+) sensor STIM1, which controls the magnitude of Ca(2+) entry. Developmental regulation of these proteins was associated with selective activation of the pathway in B cells prone to negative selection. This checkpoint was impaired in PKC-δ-deficient mice, which developed B cell autoimmunity. Conversely, overexpression of STIM1 conferred a competitive disadvantage to developing B cells. Our findings establish Ca(2+)-dependent Erk signaling as a critical proapoptotic pathway that mediates the negative selection of B cells.
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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.