THE SH3 DOMAIN OF P56(LCK) BINDS TO PROLINE-RICH SEQUENCES IN THE CYTOPLASMIC DOMAIN OF CD2

CD2, a cell surface glycoprotein expressed on T cells and natural kill er cells, can couple to signaling pathways that result in T cell proli feration. An Src-Like protein tyrosine kinase, p56(kk), coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56(kk), suggesting that an interactio n with p56(kk) contributes to CD2-mediated signaling. Herein, we inves tigate the mechanism by which CD2 associates with p56(kk). We demonstr ate that CD2 and p56(kk) associate when coexpressed in nonlymphoid cel ls, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56(kk) mediates its interactions with CD2. Usi ng truncation mutants of CD2, we identify two regions in the cytoplasm ic domain of CD2 involved in binding p56(kk). Each region contains a p roline-rich sequence that, in the form of a synthetic peptide, directl y binds p56(kk). Thus, proline-rich sequences in the cytoplasmic domai n of CD2 allow this transmembrane receptor to bind to the SH3 domain o f p56(kk).