Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system

Masakazu Takeuchi, Satomi Kuramochi, Noemi Fusaki, Shigeyuki Nada, Junko Kawamura-Tsuzuku, Satoru Matsuda, Kentaro Semba, Kumao Toyoshima, Masato Okada, Tadashi Yamamoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)


The Src-like protein-tyrosine kinase Fyn is associated with T-cell antigen receptor. Transient expression of actively mutated Fyn, having Phe-528 instead of Tyr-528 or Thr-338 instead of Ile-338, in Jurkat T-cells stimulated the serum response element (SRE), 12-O-tetradecanoylphorbol-13-acetate response element, cyclic AMP response element, and c-fos promoter. The stimulation of SRE was particularly prominent not only with active Fyn but also with normal (wild-type) Fyn. SRE was also stimulated by both normal and active Lck. Furthermore, normal and active Fyn stimulated transcription from the IL-2 gene promoter when transfected cells were stimulated by concanavalin A plus 12-O-tetradecanoylphorbol-13-acetate. Under the same conditions, Lck did not stimulate IL-2 promoter unless it was activated by mutation. Interestingly, a mutant Fyn, which has deletions within the SH2 region and so is able to transform chicken embryo fibroblasts, did not stimulate either the c-fos or IL-2 promoter, suggesting the importance of this region in T-cell signaling. Csk, which phosphorylates tyrosine residues in the negative regulatory sites of Src family kinases, down-regulated Fyn- and Lck-mediated stimulation of the serum response element and Fyn-mediated enhancement of IL-2 promoter activity. These data suggest that Fyn and Lck, whose activities are regulated by Csk, are involved in different phases of T-cell activation.

Original languageEnglish
Pages (from-to)27413-27419
Number of pages7
JournalJournal of Biological Chemistry
Issue number36
Publication statusPublished - 1993 Dec 25
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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