Characterization of p59fyn-mediated signal transduction on T cell activation

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


研究成果: Article査読

35 被引用数 (Scopus)


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.

ジャーナルInternational Immunology
出版ステータスPublished - 1994 8月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


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