SOCS-1 can suppress CD3 zeta- and Syk-mediated NF-AT activation in a non-lymphoid cell line

To elucidate T cell antigen receptor (TCR) signaling leading to activation nuclear factor of activated T cells (NF-AIT), we reconstituted TCR signalin g to activate NF-AT in a non-lymphoid cell line, 293T, We demonstrated that co-expression of CD8/zeta and Syk were neccesary for NF-AT activation in 2 93T, This NF-AT response was completely inhibited hy the addition of cyclos porin A or FK506, but markedly enhanced by the additional expression of Tee protein tyrosine kinase, We also show that the cytokine signaling suppress or, suppressor of cytokine signaling 1, potently inhibited this response by interacting with Syk and immunoreceptor tyrosine-based activation motifs i n CD8/zeta, These results imply that this novel system may provide a useful tool to delineate or identify the regulatory molecules for CD3 zeta/Syk-me diated NF-AT activation. (C) 2000 Federation of European Biochemical Societ ies.