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

M. Takeuchi, S. Kuramochi, N. Fusaki, S. Nada, J. Kawamura-Tsuzuku, S. Matsuda, K. Semba, K. Toyoshima, M. Okada, T. Yamamoto

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Abstract

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-tetradecanoyl-phorbol-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-tetradecanoyl-phorbol-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
Volume268
Issue number36
Publication statusPublished - 1993 Dec 1

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Takeuchi, M., Kuramochi, S., Fusaki, N., Nada, S., Kawamura-Tsuzuku, J., Matsuda, S., Semba, K., Toyoshima, K., Okada, M., & Yamamoto, T. (1993). Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. Journal of Biological Chemistry, 268(36), 27413-27419.