Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system.
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-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.
Takeuchi
M
M
Institute of Medical Science, University of Tokyo, Japan.
Kuramochi
S
S
Fusaki
N
N
Nada
S
S
Kawamura-Tsuzuku
J
J
Matsuda
S
S
Semba
K
K
Toyoshima
K
K
Okada
M
M
Yamamoto
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019061:src-Family Kinases
D017931:DNA Primers; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C000631346:CSK protein, human; D013755:Tetradecanoylphorbol Acetate