PMID- 10570256 OWN - NLM STAT- MEDLINE DCOM- 19991220 LR - 20190826 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 163 IP - 11 DP - 1999 Dec 1 TI - Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. PG - 5753-7 AB - SLP-76 (Src homology (SH) 2-domain-containing leukocyte protein of 76 kDa) and FYB/SLAP (FYN-T-binding protein/SLP-76-associated protein) are two hemopoietic cell-specific adaptor proteins downstream of TCR-activated protein tyrosine kinases. SLP-76 has been implicated as an essential component in T cell signaling. FYB is selectively phosphorylated by FYN-T, providing a template for the recruitment of FYN-T and SLP-76 SH2 domains. Coexpression of FYN-T, FYB, and SLP-76 can synergistically up-regulate IL-2 production in T cells upon TCR ligation. In this report, we show that two tyrosines, Tyr595 and Tyr651, of FYB are major sites of phosphorylation by FYN-T and mediate binding to SLP-76 in Jurkat T cells. Furthermore, the synergistic up-regulation of IL-2 promoter activity in the FYN-T-FYB-SLP-76 pathway is contingent upon the interaction between FYB and SLP-76, but not the interaction between FYB and FYN-T. These observations define a pathway by which SLP-76 interacts with downstream components in the up-regulation of T cell cytokine production. FAU - Geng, L AU - Geng L AD - Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Harvard Medical School, Boston, MA 02115, USA. FAU - Raab, M AU - Raab M FAU - Rudd, C E AU - Rudd CE LA - eng PT - Journal Article PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (FYB1 protein, human) RN - 0 (Interleukin-2) RN - 0 (Phosphoproteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (SLP-76 signal Transducing adaptor proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn) SB - AIM SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Motifs MH - Amino Acid Sequence MH - Carrier Proteins/*metabolism MH - Interleukin-2/*biosynthesis MH - Molecular Sequence Data MH - Phosphoproteins/*metabolism MH - Phosphorylation MH - Protein-Tyrosine Kinases/*metabolism MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-fyn MH - Receptors, Antigen, T-Cell/*metabolism MH - Sequence Homology, Amino Acid MH - Signal Transduction MH - Up-Regulation EDAT- 1999/11/26 00:00 MHDA- 1999/11/26 00:01 CRDT- 1999/11/26 00:00 PHST- 1999/11/26 00:00 [pubmed] PHST- 1999/11/26 00:01 [medline] PHST- 1999/11/26 00:00 [entrez] AID - ji_v163n11p5753 [pii] PST - ppublish SO - J Immunol. 1999 Dec 1;163(11):5753-7.