The SH 3 D o m a i n o f p 56 lck Binds to Proline - rich Sequences in the Cytoplasmic D o m a i n o f CD

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p50 ok, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56 kk, suggesting that an interaction with p56 l~k contributes to CD2mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p561ok. We demonstrate that CD2 and p56 l~k associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p561ok mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasnfic domain of CD2 involved in binding p56 kk. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56 lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p561ok.