ArticleMolecular and cellular biology1995
Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.
Article in Molecular and cellular biology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 144 citations in OpenAlex.
- Costimulation loss enhances IL-2-driven Treg generation by PI3K-STAT3 inhibition in CNS autoimmunity.EMBO molecular medicine · 2026Article
- Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.Science advances · 2021Article
- PI3K Orchestrates T Follicular Helper Cell Differentiation in a Context Dependent Manner: Implications for Autoimmunity.Frontiers in immunology · 2018Review
- Fluoxetine induces alkalinization of astroglial cytosol through stimulation of sodium-hydrogen exchanger 1: dissection of intracellular signaling pathways.Frontiers in cellular neuroscience · 2015Article
- PI3K pathway inhibitors: potential prospects as adjuncts to vaccine immunotherapy for glioblastoma.Immunotherapy · 2014Review
- Insulin stimulates translocation of human GLUT4 to the membrane in fat bodies of transgenic Drosophila melanogaster.PloS one · 2013Article
- Integrating signals from the T-cell receptor and the interleukin-2 receptor.PLoS computational biology · 2011Article
- Protein phosphatase 2A regulates interleukin-2 receptor complex formation and JAK3/STAT5 activation.The Journal of biological chemistry · 2010Article
- PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk.Molecular systems biology · 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
- PIP3 pathway in regulatory T cells and autoimmunity.Immunologic research · 2007Review
- Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets.Journal of translational medicine · 2006Article
- Phosphatidylinositol 3-kinase mediates activation of ATM by high NaCl and by ionizing radiation: Role in osmoprotective transcriptional regulation.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- IL-2- and STAT5-regulated cytokine gene expression in cells expressing the Tax protein of HTLV-1.Oncogene · 2005Article
- Gap junctions regulate extracellular signal-regulated kinase signaling to affect gene transcription.Molecular biology of the cell · 2005Article
- ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells.Journal of immunology (Baltimore, Md. : 1950) · 2004Article
- Signal-transduction defects in T cells.Clinical reviews in allergy & immunology · 2001Review
- Involvement of phosphoinositide-3-kinase and p70 S6 kinase in regulation of proliferation of rat lactotrophs in culture.Endocrine · 2000Article
- Phosphatidylinositol 3-kinase, protein kinase B and ribosomal S6 kinases in the stimulation of thyroid epithelial cell proliferation by cAMP and growth factors in the presence of insulin.The Biochemical journal · 2000Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Phosphatidylinositol 3-kinase (PI3-K) has been implicated as a signal-transducing component in interleukin-2 (IL-2)-induced mitogenesis. However, the function of this lipid kinase in regulating IL-2-triggered downstream events has remained obscure. Using the potent and specific PI3-K inhibitor, wortmannin, we assessed the role of PI3-K in IL-2-mediated signaling and proliferation in the murine T-cell line CTLL-2. Addition of the drug to exponentially growing cells resulted in an accumulation of cells in the G0/G1 phase of the cell cycle. Furthermore, wortmannin also partially suppressed IL-2-induced S-phase entry in G1-synchronized cells. Analysis of IL-2-triggered signaling pathways revealed that wortmannin pretreatment resulted in complete inhibition of IL-2-provoked p70 S6 kinase activation and also attenuated IL-2-induced MAP kinase activation at drug concentrations identical to those required for inhibition of PI3-K catalytic activity. Wortmannin also diminished the IL-2-triggered activation of the MAP kinase activator, MEK, but did not inhibit activation of Raf, the canonical upstream activator of MEK. These results suggest that a novel wortmannin-sensitive activation pathway regulates MEK and MAP kinase in IL-2-stimulated T lymphocytes.
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