ArticleProceedings of the National Academy of Sciences of the United States of America1997
The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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.
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Who cites it
52 citing papers in PubMed, 145 citations in OpenAlex.
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- Case Report: Mutations inFrontiers in immunology · 2022Article
- Transcriptome Analysis Reveals Key miRNA-mRNA Pathways in Ovarian Tissues of Yunshang Black Goats With Different Kidding Numbers.Frontiers in endocrinology · 2022Article
- Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation.Inflammopharmacology · 2021Review
- Deregulation of the Interleukin-7 Signaling Pathway in Lymphoid Malignancies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Essential Kinases and Transcriptional Regulators and Their Roles in Autoimmunity.Biomolecules · 2019Review
- The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects.Frontiers in endocrinology · 2018Review
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
- The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.Frontiers in endocrinology · 2017Review
- Differential regulation of Janus kinase 3 (JAK3) in bovine preovulatory follicles and identification of JAK3 interacting proteins in granulosa cells.Journal of ovarian research · 2016Article
- JAK kinase targeting in hematologic malignancies: a sinuous pathway from identification of genetic alterations towards clinical indications.Haematologica · 2015Review
- Combined immunodeficiency evolving into predominant CD4+ lymphopenia caused by somatic chimerism in JAK3.Journal of clinical immunology · 2014Article
- Structural basis of recognition of interferon-α receptor by tyrosine kinase 2.Nature structural & molecular biology · 2014Article
- Integrating non-coding RNAs in JAK-STAT regulatory networks.JAK-STAT · 2014Review
- Janus kinase inhibitors in autoimmune diseases.Annals of the rheumatic diseases · 2013Review
- Janus kinase 3: the controller and the controlled.Acta biochimica et biophysica Sinica · 2012Review
- MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells.Oncogene · 2012Article
- 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
- Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies.Genes & cancer · 2010Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
JAK3 is a protein tyrosine kinase that specifically associates with the common gamma chain (gammac), a shared subunit of receptors for interleukin (IL) 2, 4, 7, 9, and 15. Patients deficient in either JAK3 or gammac presented with virtually identical forms of severe combined immunodeficiency (SCID), underscoring the importance of the JAK3-gammac interaction. Despite the key roles of JAK3 and gammac in lymphocytic development and function, the molecular basis of this interaction remains poorly understood. In this study, we have characterized the regions of JAK3 involved in gammac association. By developing a number of chimeric JAK3-JAK2 constructs, we show that the binding specificity to gammac can be conferred to JAK2 by transferring the N-terminal domains of JAK3. Moreover, those JAK3-JAK2 chimeras capable of binding gammac were also capable of reconstituting IL-2 signaling as measured by inducible phosphorylation of the chimeric JAK3-JAK2 protein, JAK1, the IL-2 receptor beta chain, and signal transducer and activator of transcription 5A. Subsequent deletion analyses of JAK3 have identified the N-terminal JH7-6 domains as a minimal region sufficient for gammac association. Furthermore, expression of the mutant containing only the JH7-6 domains effectively competed with full-length JAK3 for binding to gammac. We conclude that the JH7-6 domains of JAK3 are necessary and sufficient for gammac association. These studies offer clues toward a broader understanding of JAK-mediated cytokine signaling and may provide a target for the development of novel therapeutic modalities in immunologically mediated diseases.
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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.