The SH3 domain of p56(lck) binds to proline-rich sequences in the cytoplasmic domain of CD2

被引:82
作者
Bell, GM [1 ]
Fargnoli, J [1 ]
Bolen, JB [1 ]
Kish, L [1 ]
Imboden, JB [1 ]
机构
[1] BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL,PRINCETON,NJ 08543
关键词
D O I
10.1084/jem.183.1.169
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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, 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 interaction with p56(kk) contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56(kk). We demonstrate that CD2 and p56(kk) associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56(kk) mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic 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(kk). Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56(kk).
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页码:169 / 178
页数:10
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