Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation.
An intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two PPPGHR segments within the cytoplasmic region of CD2, was identified. Mutagenesis and NMR analysis demonstrated that the CD2 binding region of CD2BP2 includes a 17-aa motif (GPY[orF]xxxxM[orV]xxWxxx GYF), also found in several yeast and Caenorhabditis elegans proteins of unknown function. In Jurkat T cells, over-expression of the isolated CD2BP2 domain binding to CD2 enhances the production of interleukin 2 on crosslinking of CD2 but not the T cell receptor. Hence, a proline-binding module distinct from SH3 and WW domains regulates protein-protein interactions.
Nishizawa
K
K
Laboratory of Immunobiology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Freund
C
C
Li
J
J
Wagner
G
G
Reinherz
E L
EL
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018801:CD2 Antigens / Q000235:genetics / Q000276:immunology*; D017173:Caenorhabditis elegans; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004252:DNA Mutational Analysis; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011392:Proline; D012441:Saccharomyces cerevisiae; D017421:Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens; C120378:CD2BP2 protein, human; D002352:Carrier Proteins; D011392:Proline