ArticleMolecular and cellular biology2002
Stat6 and IRS-2 cooperate in interleukin 4 (IL-4)-induced proliferation and differentiation but are dispensable for IL-4-dependent rescue from apoptosis.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 87 citations in OpenAlex.
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- Transcription factor signal transducer and activator of transcription 6 (STAT6) is an inhibitory factor for adult myogenesis.Skeletal muscle · 2021Article
- IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.Frontiers in immunology · 2018Review
- Increased levels of Gab1 and Gab2 adaptor proteins skew interleukin-4 (IL-4) signaling toward M2 macrophage-driven pulmonary fibrosis in mice.The Journal of biological chemistry · 2017Article
- The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling.Oncotarget · 2017Article
- The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.Science signaling · 2016Article
- Breaking Free of Control: How Conventional T Cells Overcome Regulatory T Cell Suppression.Frontiers in immunology · 2016Review
- Impact of Enriched Environment on Murine T Cell Differentiation and Gene Expression Profile.Frontiers in immunology · 2016Article
- CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.PLoS pathogens · 2015Article
- Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).International journal of molecular medicine · 2015Review
- Article
- IL-4: an important cytokine in determining the fate of T cells.Biophysical reviews · 2014Review
- CD4+ T cell subset differentiation and avidity setpoint are dictated by the interplay of cytokine and antigen mediated signals.PloS one · 2014Article
- Dynamic modularity of host protein interaction networks in Salmonella Typhi infection.PloS one · 2014Article
- The potential for genetically altered microglia to influence glioma treatment.CNS & neurological disorders drug targets · 2013Review
- The TSC-mTOR pathway regulates macrophage polarization.Nature communications · 2013Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Stat6 and IRS-2 are two important signaling proteins that associate with the cytoplasmic tail of the interleukin 4 (IL-4) receptor. Data from numerous in vitro experiments have led to a model for IL-4 signal transduction in which the Stat6 signaling pathway is responsible for the IL-4 induced changes in gene expression and differentiation events, while the IRS-2 signaling pathway provides mitogenic and antiapoptotic signals. In order to determine the relative contributions of these signaling molecules in primary lymphocytes, we have examined IL-4 responses in T cells from mice deficient for either Stat6 or IRS-2 as well as from mice doubly deficient for both genes. Both IRS-2 and, especially, Stat6 are shown to be critically involved in IL-4-induced proliferation of T cells, presumably through the cooperative regulation of the Cdk inhibitor p27kip1. Like Stat6-deficient Th cells, IRS-2-deficient cells are also compromised in their ability to secrete Th2 cytokines, revealing a previously unrecognized role for IRS-2 in Th2 cell development. Although Stat6 and/or IRS-2 expression is required for IL-4-induced proliferative and differentiative responses, both signaling proteins are dispensable for the antiapoptotic effect of IL-4. However, treatment of lymphocytes with a protein tyrosine phosphatase inhibitor is able to block the antiapoptotic effect of IL-4 specifically in Stat6- or IRS-2-deficient cells and not in wild-type cells. Our results suggest that Stat6 and IRS-2 cooperate in promoting both IL-4-induced proliferative and differentiating responses, while an additional signaling mediator that depends on protein tyrosine phosphatase activity contributes to the antiapoptotic activities of IL-4 in primary T cells.
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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.