ArticleThe EMBO journal1999
Autosomal SCID caused by a point mutation in the N-terminus of Jak3: mapping of the Jak3-receptor interaction domain.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 115 citations in OpenAlex.
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Case report: A novelFrontiers in immunology · 2024Article
- Article
- Case Report: Mutations inFrontiers in immunology · 2022Article
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors.Pharmacological research · 2019Review
- Evaluating tofacitinib citrate in the treatment of moderate-to-severe active ulcerative colitis: design, development and positioning of therapy.Clinical and experimental gastroenterology · 2019Review
- The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects.Frontiers in endocrinology · 2018Review
- Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.Leukemia · 2017Review
- JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects.Drugs · 2017Review
- The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.Frontiers in endocrinology · 2017Review
- Crystal Structure of the FERM-SH2 Module of Human Jak2.PloS one · 2016Article
- Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor Specificities.The Journal of biological chemistry · 2015Article
- Article
- Structural basis of recognition of interferon-α receptor by tyrosine kinase 2.Nature structural & molecular biology · 2014Article
- Biology and significance of the JAK/STAT signalling pathways.Growth factors (Chur, Switzerland) · 2012Review
- Phosphorylation of Y372 is critical for Jak2 tyrosine kinase activation.Cellular signalling · 2011Article
- FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma.Blood · 2011Article
- The use of structural biology in Janus kinase targeted drug discovery.Current drug targets · 2011Review
- Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases.Journal of cellular and molecular medicine · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Signaling through the hematopoietic receptors requires activation of receptor-associated Janus (Jak) kinases. For example, Jak1 and Jak3 bind specifically to the IL-2 receptor beta (IL-2Rbeta) and common gamma (gammac) chains, respectively, and initiate biochemical signals critical in controlling immune responses. The region of Jak responsible for receptor interactions, however, is not well characterized. Here we describe a naturally occurring Jak3 mutation from a patient with autosomal severe combined immunodeficiency (SCID), where a single amino acid substitution, Y100C, in Janus homology domain 7 (JH7) prevents kinase-receptor interaction. This mutation also results in a loss of IL-2-induced signaling in a B-cell line derived from this patient. Using mutational analysis we have identified a region of Jak3, including portions of JH6 and JH7, that is sufficient for kinase-receptor contact and show that this segment interacts with the proline-rich Box1 region of the receptor. Furthermore, a Jak3-Jak1 chimera containing only the JH6 and JH7 domains of Jak3 interacts with gammac and can reconstitute IL-2-dependent responses, including receptor phosphorylation and activation of signal transducer and activator of transcription (STAT) 5b. Our results suggest that the N-terminus of Jak kinases is critical for receptor binding, and is therefore likely to determine specificity of Jak kinase-receptor interactions.
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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.