ArticleProceedings of the National Academy of Sciences of the United States of America2014
Adaptor protein DOK3 promotes plasma cell differentiation by regulating the expression of programmed cell death 1 ligands.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.Acta pharmaceutica Sinica. B · 2025Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Expression and clinical significance of DOK3 in renal clear cell carcinoma.The Journal of international medical research · 2023Article
- The RNA-binding protein hnRNP F is required for the germinal center B cell response.Nature communications · 2023Article
- A Novel Integrated Metabolism-Immunity Gene Expression Model Predicts the Prognosis of Lung Adenocarcinoma Patients.Frontiers in pharmacology · 2021Article
- DOK3 is involved in microglial cell activation in neuropathic pain by interacting with GPR84.Aging · 2020Article
- Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer.International journal of molecular sciences · 2020Review
- Emerging Roles of Downstream of Kinase 3 in Cell Signaling.Frontiers in immunology · 2020Review
- Dok3-protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity.The Journal of clinical investigation · 2019Article
- Transcription factor YY1 is essential for iNKT cell development.Cellular & molecular immunology · 2019Article
- Harnessing immunotherapy for liver recipients with hepatocellular carcinoma: a review from a transplant oncology perspective.Therapeutic advances in medical oncology · 2019Review
- A functional genomics predictive network model identifies regulators of inflammatory bowel disease.Nature genetics · 2017Article
- PD-1 and its ligands are important immune checkpoints in cancer.Oncotarget · 2017Review
- Article
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adaptor Downstream-of-Kinase (DOK) 3 functions as a negative regulator and attenuates B-cell receptor-mediated calcium signaling. Although DOK3 is dispensable for early B-cell development, its role in plasma cell (PC) differentiation is unknown. Here, we show that Dok3(-/-) mice have increased populations of T follicular-helper (Tfh) and germinal center (GC) B cells upon immunization with a T-cell-dependent antigen. However, interestingly, they generate significantly fewer PCs. Bone marrow reconstitution experiments show that the PC defect is B-cell intrinsic and due to the inability of Dok3(-/-) B cells to sustain programmed cell death 1 (PD-1) ligand 1 (PDL1) and up-regulate PD-1 ligand 2 (PDL2) expressions that are critical for PC differentiation. Overexpression of PDL2 rectifies the PC differentiation defect in Dok3(-/-) B cells. We further demonstrate that calcium signaling suppresses the transcription of PD-1 ligands. Abrogation of calcium signaling in B cells by deleting BTK or PLCγ2 or inhibiting calcineurin with cyclosporine A leads to increased expression of PD-1 ligands. Thus, our study reveals DOK3 as a nonredundant regulator of PC differentiation by up-regulating PD-1 ligand expression through the attenuation of calcium signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.