The src-family kinase, fyn, regulates the activation of phosphatidyllnositol 3-kinase in an interleukin 2-responsive t cell line

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

Research output: Contribution to journalArticle

71 Scopus citations

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 ryrosine kinase (FFK) activity. One IL-2-regulated FTK 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 wildtype Fyn in these cells enhanced both the basal and IL-2-mediated activation of PD-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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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