FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells.
Protein-tyrosine kinases p56(Lck), SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential components in T-cell activation. Another lymphoid-specific adaptor FYB/SLAP has also been identified as a predominant binding partner of SLP-76 and the Src kinase FYN-T, although its role in the activation process has been unclear. In this study, we demonstrate that FYN-T selectively phosphorylates FYB providing a template for the recruitment of FYN-T and SLP-76 SH2 domain binding. This interaction is unusual in its distinct cytoplasmic localization and its long term stable kinetics of phosphorylation. Furthermore, we demonstrate for the first time that the co-expression of all three components of the FYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cell receptor-driven interleukin 2 transcription activity. These findings document the existence of a T-cell receptor-regulated FYN-T-FYB pathway that interfaces with the adaptor SLP-76 and up-regulates lymphokine production in T-cells.
Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
M
M
Raab
H
H
Kang
A
A
da Silva
X
X
Zhu
C E
CE
Rudd
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; D007376:Interleukin-2; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases