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 activ ation. Another lymphoid-specific adaptor FYB/SLAP has also been identified as a predominant binding partner of SLP-76 and the Src kinase FYN-T, althou gh its role in the activation process has been unclear. Inthis study, we de monstrate that FYN-T selectively phosphorylates FYB providing a template fo r the recruitment of FYN-T and SLP-76 SH2 domain binding. This interaction is unusual in its distinct cytoplasmic localization and its long term stabl e kinetics of phosphorylation. Furthermore, we demonstrate for the first ti me that the co-expression of all three components of the FYN-T-FYB-SLP-76 m atrix can synergistically up-regulate T-cell receptor-driven interleukin 2 transcription activity. These findings document the existence of a T-cell r eceptor-regulated FYN-T-FYB pathway that interfaces with the adaptor SLP-76 and cap-regulates lymphokine production in T-cells.