THE PROTEIN-TYROSINE KINASE FYN ACTIVATES TRANSCRIPTION FROM THE HIV PROMOTER VIA ACTIVATION OF NF-KAPPA-B-LIKE DNA-BINDING PROTEINS

Protein tyrosine kinase p59(fyn) (Fyn) associates with the TCR-CD3 complex, which suggests that Fyn plays a significant role in the signal transduction involving TCR complex, In addition to cellular genes, viral promoters such as the HIV long terminal repeat (LTR) are also activated upon T cell activation, To elucidate the functional significance of Fyn in the expression of viral promoters, we transfected a Fyn-expression vector together with a reporter plasmid containing the chloramphenicol acetyltransferase gene driven by HIV LTR into a human T cell line, Jurkat, In this assay, Fyn stimulated the promoter in HIV LTR when the transfected cells were treated with both concanavalin A and PMA as an antigen-mimic stimulation, This activation required the intact SH2 domain of Fyn, Mutational analysis of HIV LTR showed that the NF kappa B binding sites were responsible for this effect, Electrophoretic mobility shift assays and UV cross-linking experiments showed that activation of T cells by anti-CD3 antibody induced four kappa B-binding proteins (50, 60, 65 and 100 kDa) in Fyn-overexpressing cells more efficiently than in the parental cells, Our results suggested that Fyn was able to regulate expression of a subset of genes via kappa B-binding proteins upon T cell activation.