3 DOMAINS OF SLP-76 ARE REQUIRED FOR ITS OPTIMAL FUNCTION IN A T-CELLLINE

We and others have shown that overexpression of SLP-76 augments TCR-st imulated IL-2 promoter activity in the Jurkat T cell line. In this rep ort we investigate the signaling mechanisms through which SLP-76 media tes its effect on T cell activation. We show that overexpressed SLP-76 acts downstream of TCR-stimulated protein tyrosine kinases, but does not affect calcium signaling. Overexpression of SLP-76 does, however, augment TCR stimulation of both ERK (extracellular signal-regulated ki nase) activity and a reporter construct driven by activating protein-1 binding sites. Structure/function analysis reveals that three distinc t regions of SLP-76, each important for protein associations, are requ ired for augmentation of TCR-induced nuclear factor-AT activity. These data suggest that SLP-76 functions as an adapter molecule that requir es three unique domains to link proximal TCR signals in T cells.