ArticleMolecular and cellular biology1996
A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 68 citations in OpenAlex.
- The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype.Clinical and experimental immunology · 2020Article
- Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes.Molecular & cellular proteomics : MCP · 2016Article
- Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes.Scientific reports · 2016Article
- The common γ-chain cytokine receptor: tricks-and-treats for T cells.Cellular and molecular life sciences : CMLS · 2016Review
- The extracellular and transmembrane domains of the γC and interleukin (IL)-13 receptor α1 chains, not their cytoplasmic domains, dictate the nature of signaling responses to IL-4 and IL-13.The Journal of biological chemistry · 2012Article
- Cell cycle progression following naive T cell activation is independent of Jak3/common gamma-chain cytokine signals.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Differential regulation of the IL-17 receptor by gammac cytokines: inhibitory signaling by the phosphatidylinositol 3-kinase pathway.The Journal of biological chemistry · 2008Article
- JAKs, STATs and Src kinases in hematopoiesis.Oncogene · 2002Review
- Enhanced signaling through the IL-2 receptor in CD8+ T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Janus kinases: components of multiple signaling pathways.Oncogene · 2000Review
- Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Autosomal SCID caused by a point mutation in the N-terminus of Jak3: mapping of the Jak3-receptor interaction domain.The EMBO journal · 1999Article
- Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction.Molecular medicine (Cambridge, Mass.) · 1998Review
- Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.Genes & development · 1998Article
- Severe combined immune deficiencies due to defects of the common gamma chain-JAK3 signaling pathway.Springer seminars in immunopathology · 1998Review
- 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.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Requirement for an initial signal from the membrane-proximal region of the interleukin 2 receptor gamma(c) chain for Janus kinase activation leading to T cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Immunotoxin therapy for CNS tumor.Journal of neuro-oncologyReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c critical to this process, mutations were introduced into the cytoplasmic domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are activated by granulocyte-macrophage colony-stimulating factor. Whereas previous studies of fibroblasts and transformed T cells have suggested that signalling by gamma c requires both membrane-proximal and C-terminal subdomains, our results for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids are sufficient to mediate a normal proliferative response, including induction of the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on tyrosine upon receptor activation and could potentially interact with downstream molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable for mitogenic signalling. However, deletion of a membrane-proximal region conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an adjacent region unique to gamma c (residues 40 to 52) abrogated functional interaction of the receptor chain with the tyrosine kinase Jak3. This correlated with a loss of all signalling events analyzed, including phosphorylation of the IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction of the proliferative response. Thus, it appears in T cells that Jak3 is a critical mediator of mitogenic signaling by the gamma c chain.
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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.