ArticleProceedings of the National Academy of Sciences of the United States of America1995
Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 446 citations in OpenAlex.
- Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.Cell host & microbe · 2017Trial
- Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12.The Journal of clinical investigation · 1998Trial
- RAS P21 Protein Activator 3 finetunes Type I immunity by limiting HCK-mediated STAT4 phosphorylation.Nature communications · 2026Article
- Inflame and restrain - the paradoxical roles of IL-12 and IL-23 in immunity.Nature reviews. Immunology · 2026Review
- Cell-Intrinsic Type I Interferon Signaling as a Pleiotropic Orchestrator of CD4 T Cell Immunity.Biomolecules · 2026Review
- IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy.Immunity · 2026Article
- Intratumoral delivery of 4-1BBL boosts IL-12-triggered anti-glioma immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- An Immunomodulating Peptide with Potential to Promote Anticancer Immunity Without Compromising Immune Tolerance.Biomedicines · 2025Article
- The Differential Expression of the JAK/STAT Pathway in Breast Cancer Cells Transfected with Human Papillomavirus Oncogenes.Viruses · 2025Article
- Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4＋ T cells.BMB reports · 2025Review
- The CXCR6-CXCL16 axis mediates T cell control of polyomavirus infection in the kidney.PLoS pathogens · 2025Article
- Harnessing the Potential of FAP-IL12mut TMEkine for Targeted and Enhanced Antitumor Responses.Molecular cancer therapeutics · 2025Article
- Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development.Biological research · 2024Article
- A Transcriptomic Analysis of Laryngeal Dysplasia.International journal of molecular sciences · 2024Review
- A review of CD4Veterinary immunology and immunopathology · 2024Review
- IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.Nature communications · 2024Article
- XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.Molecular cancer therapeutics · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
- STAT4 gene polymorphisms in human diseases.Frontiers in immunology · 2024Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily. We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2, implicating these kinases in the immediate biochemical response to IL-12. Recently, transcription factors known as STATs (signal transducers and activators of transcription) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases. In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4. These data, and the recent demonstration of JAK phosphorylation by IL-12, identify a rapid signal-transduction pathway likely to mediate IL-12-induced gene expression.
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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.