The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line

Larry M Karnitz, Shari L. Sutor, Robert T. Abraham

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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.

Original languageEnglish (US)
Pages (from-to)1799-1808
Number of pages10
JournalJournal of Experimental Medicine
Volume179
Issue number6
DOIs
StatePublished - Jun 1 1994

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Phosphatidylinositol 3-Kinase
src-Family Kinases
Interleukin-2
T-Lymphocytes
Cell Line
Protein-Tyrosine Kinases
Phosphorylation
src Homology Domains
Tyrosine
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Immunology

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The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line. / Karnitz, Larry M; Sutor, Shari L.; Abraham, Robert T.

In: Journal of Experimental Medicine, Vol. 179, No. 6, 01.06.1994, p. 1799-1808.

Research output: Contribution to journalArticle

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