Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production

T-cell activation involves the participation of protein-tyrosine kinases p5 6(lck) and ZAP-70/SYK. as well as lymphoid proteins such as SLP-76 and FYB/ SLAP. FYB/SLAP has the hallmarks of an adaptor protein that binds to the SH 2 domains of the Src kinase FYN-T and SLP-76, Whereas two forms of FYB at 1 20 and 130 kDa have been identified biochemically, a cDNA encoding only the lower molecular weight isoform has been cloned (termed FYB-120 or SLAP-130 ), In this study, we report the isolation of an alternative isoform of FYB with a molecular mass of 130 kDa (FYB-130) that has the same structure as F YB-130 except for an insertion of 46 amino acids toward the carboxyl-termin al region of the protein. FYB-120 and FYB-130 share an ability to bind to t he SH2 domains of FYN-T and SLP-76, to act as substrates for p59(FYN-T), an d to be expressed in the cytoplasm and nucleus of T-cells, Differences were noted between the isoforms in the efficiency of binding to SLP-76 and in t he preferential expression of FYB-130 in mature T-cells. When co-expressed together with FYN-T and SLP-76, FYB-130 caused a significant increase in an ti-CD3-driven NF-AT transcription. Finally, fluorescence in situ hybridizat ion analysis localized the FYB gene to human chromosome 5 at position p13.1 . FYB-130 therefore represents a novel variant of FYB protein that can up-r egulate T-cell receptor-driven interleukin 2 production in mature T-cells.