Characterization of p59fyn-mediated signal transduction on T cell activation

Noemi Fusaki, Kentaro Senba, Takuya Katagiri, Gen Suzuki, Satoru Matsuda, Tadashi Yamamoto

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34 Citations (Scopus)

Abstract

Protein tyrosine kinase p59fyn is associated with the TCR - CD3 complex and is suggested to play a role in T cell activation. To determine the molecular mechanism of p59fyn-medlated signal transduction in T cell activation, we established murine T cell hybridoma lines that expressed an elevated amount of wild-type or mutant fyn. Clones that expressed high levels of normal p59fyn and active p59fyn, encoded by wild-type and f-14 mutant fyn respectively, showed enhanced IL-2 production upon stimulation by anti-CD3 antibodies or natural antigen. On the other hand, clones that expressed kinase negative p59fyn and p59fyn with an SH2 (Src-homology 2) deletion encoded by t-1 mutant fyn showed little induction of IL-2 production upon stimulation. These data suggest that p59fyn is important in T cell signaling and that the SH2 sequence plays a critical role in the reaction. Induction of tyrosine phosphorylatlon of multiple proteins upon antigenic stimulation was augmented similarly in the cells that respectively expressed wild-type and f-14 mutant fyn at elevated levels. The proteins that became highly tyrosine-phosphorylated included phospholipase C (PLC-γ1), P95vav, ZAP-70, the MAP kinase, CD3ζ and unidentified proteins of 120, 100 and 80 kDa. Tyrosine phosphorylation of the 120, 95 and 68 kDa proteins associated with PLC-γ1 was also observed in these cells upon stimulation. In contrast, only the 100 kDa protein and the MAP kinase were increasingly tyrosine phosphorylated in the antigen-stimulated cells expressing t-1 fyn. These data suggest that PLC-γ1, PLC-γ1 associated molecules, p95vav, the 80 kDa protein, ZAP-70 and the CD3ζ chain may be substrates of p59fyn or of other tyrosine kJnases regulated by p59fyn and be important in T cell signaling.

Original languageEnglish
Pages (from-to)1245-1255
Number of pages11
JournalInternational Immunology
Volume6
Issue number8
DOIs
Publication statusPublished - 1994 Aug
Externally publishedYes

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Keywords

  • P59fyn
  • Protein tyrosine kinase
  • Src-homology region 2
  • T cell activation
  • ZAP-70

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation
  • Immunology

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