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 Senba, Kumao Toyoshima, Masato Okada, Tadashi Yamamoto

Research output: Contribution to journalArticle

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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-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
Volume268
Issue number36
Publication statusPublished - 1993 Dec 25
Externally publishedYes

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Serum Response Element
Cell signaling
T-cells
Interleukin-2
T-Lymphocytes
src-Family Kinases
Response Elements
Tetradecanoylphorbol Acetate
Acetates
Jurkat Cells
Transcription
Fibroblasts
Concanavalin A
T-Cell Antigen Receptor
Cyclic AMP
Protein-Tyrosine Kinases
Tyrosine
Chickens
Embryonic Structures
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Takeuchi, M., Kuramochi, S., Fusaki, N., Nada, S., Kawamura-Tsuzuku, J., Matsuda, S., ... 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.

Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. / Takeuchi, Masakazu; Kuramochi, Satomi; Fusaki, Noemi; Nada, Shigeyuki; Kawamura-Tsuzuku, Junko; Matsuda, Satoru; Senba, Kentaro; Toyoshima, Kumao; Okada, Masato; Yamamoto, Tadashi.

In: Journal of Biological Chemistry, Vol. 268, No. 36, 25.12.1993, p. 27413-27419.

Research output: Contribution to journalArticle

Takeuchi, M, Kuramochi, S, Fusaki, N, Nada, S, Kawamura-Tsuzuku, J, Matsuda, S, Senba, 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, vol. 268, no. 36, pp. 27413-27419.
Takeuchi M, Kuramochi S, Fusaki N, Nada S, Kawamura-Tsuzuku J, Matsuda S et al. Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. Journal of Biological Chemistry. 1993 Dec 25;268(36):27413-27419.
Takeuchi, Masakazu ; Kuramochi, Satomi ; Fusaki, Noemi ; Nada, Shigeyuki ; Kawamura-Tsuzuku, Junko ; Matsuda, Satoru ; Senba, Kentaro ; Toyoshima, Kumao ; Okada, Masato ; Yamamoto, Tadashi. / Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 36. pp. 27413-27419.
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