ArticleThe Journal of experimental medicine1994
The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line.
Article in The Journal of experimental medicine, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 75 citations in OpenAlex.
- Basal phosphorylation of SHIP1 by Lyn suppresses proinflammatory signaling in the absence of a phagocytic synapse.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Common gamma chain cytokines in combinatorial immune strategies against cancer.Immunology letters · 2016Review
- Distinct pathways regulate Syk protein activation downstream of immune tyrosine activation motif (ITAM) and hemITAM receptors in platelets.The Journal of biological chemistry · 2015Article
- The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells.Frontiers in immunology · 2015Review
- Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells.Nature immunology · 2013Article
- Phase I pharmacokinetic and pharmacodynamic study of the pan-PI3K/mTORC vascular targeted pro-drug SF1126 in patients with advanced solid tumours and B-cell malignancies.European journal of cancer (Oxford, England : 1990) · 2012Article
- Role of Fyn and PI3K in H2O2-induced inhibition of apical Cl-/OH- exchange activity in human intestinal epithelial cells.The Biochemical journal · 2008Article
- Activation of T cells by cross-linking Qa-2, the ped gene product, requires Fyn.American journal of reproductive immunology (New York, N.Y. : 1989) · 2007Article
- IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- The Src-family tyrosine kinase inhibitor PP1 interferes with the activation of ribosomal protein S6 kinases.The Biochemical journal · 2002Article
- Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase.The EMBO journal · 2001Article
- A human class II MHC-derived peptide antagonizes phosphatidylinositol 3-kinase to block IL-2 signaling.The Journal of clinical investigation · 2000Article
- Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation.Molecular and cellular biology · 1998Article
- Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- IL-2 gene therapy of solid tumors: an approach for the prevention of signal transduction defects in T cells.Journal of molecular medicine (Berlin, Germany) · 1996Review
- Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase and inhibits a subset of responses induced by Fc epsilon R1 cross-linking.Molecular biology of the cell · 1995Article
- Formation of simian immunodeficiency virus long terminal repeat circles in resting T cells requires both T cell receptor- and IL-2-dependent activation.The Journal of experimental medicine · 1995Article
- Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.Molecular and cellular biology · 1995Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The proliferation of antigen-activated T cells is mediated by the T cell-derived growth factor, interleukin 2 (IL-2). The biochemical signaling cascades initiating IL-2-induced growth are dependent upon protein tyrosine kinase (PTK) activity. One IL-2-regulated PTK implicated in this cascade is the Src-family kinase, Fyn. Previous studies have described a physical association between Fyn and a potential downstream substrate, phosphatidylinositol 3-kinase (PI3-kinase) as well as the IL-2-dependent activation of PI3-kinase in T cells; however, the role of Fyn in IL-2-induced PI3-kinase activation remains unclear. In this report, we demonstrate that IL-2 stimulation triggers tyrosine phosphorylation of the p85 subunit of PI3-kinase in the murine T cell line, CTLL-2. Lysates prepared from growth factor-deprived and IL-2-stimulated T cells reconstituted both the binding of CTLL-2 cell-derived Fyn to and the IL-2-inducible tyrosine phosphorylation of exogenously added recombinant p85. Furthermore, overexpression of wild-type Fyn in these cells enhanced both the basal and IL-2-mediated activation of PI3-kinase. Additional studies of the Fyn-PI3-kinase interaction demonstrated that the Src homology 3 (SH3) domain of Fyn constitutes a direct binding site for the p85 subunit of PI3-kinase. These results support the notion that Fyn may be directly involved in the activation of the downstream signaling enzyme, PI3-kinase, in IL-2-stimulated T cells.
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