PMID- 10409671 OWN - NLM STAT- MEDLINE DCOM- 19990826 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 30 DP - 1999 Jul 23 TI - 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. PG - 21170-9 AB - 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. FAU - Raab, M AU - Raab M AD - Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Kang, H AU - Kang H FAU - da Silva, A AU - da Silva A FAU - Zhu, X AU - Zhu X FAU - Rudd, C E AU - Rudd CE LA - eng PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CD3 Complex) RN - 0 (Interleukin-2) RN - 0 (Phosphoproteins) RN - 0 (SLP-76 signal Transducing adaptor proteins) RN - 42HK56048U (Tyrosine) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - CD3 Complex/*metabolism MH - Enzyme Activation MH - Humans MH - Interleukin-2/*biosynthesis/genetics/immunology MH - Jurkat Cells MH - Lymphocyte Activation MH - Mice MH - Phosphoproteins/metabolism MH - Phosphorylation MH - *Protein-Tyrosine Kinases/*metabolism MH - Signal Transduction/*immunology MH - T-Lymphocytes/immunology/*metabolism MH - Transcription, Genetic MH - Tyrosine/metabolism MH - Up-Regulation EDAT- 1999/07/20 00:00 MHDA- 1999/07/20 00:01 CRDT- 1999/07/20 00:00 PHST- 1999/07/20 00:00 [pubmed] PHST- 1999/07/20 00:01 [medline] PHST- 1999/07/20 00:00 [entrez] AID - 10.1074/jbc.274.30.21170 [doi] AID - S0021-9258(19)72560-5 [pii] PST - ppublish SO - J Biol Chem. 1999 Jul 23;274(30):21170-9. doi: 10.1074/jbc.274.30.21170.