The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.
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, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck.
Bell
G M
GM
Department of Medicine, Veterans Affairs Medical Center, San Francisco, California, USA.
Fargnoli
J
J
Bolen
J B
JB
Kish
L
L
Imboden
J B
JB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D007376:Interleukin-2 / Q000096:biosynthesis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000378:metabolism; D011392:Proline; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D018411:Spodoptera / Q000166:cytology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D018801:CD2 Antigens; D007376:Interleukin-2; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D011392:Proline; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases