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 un known function. In Jurkat T cells, over-expression of the isolated CD2BP2 d omain binding to CD2 enhances the production of interleukin 2 on crosslinki ng of CD2 but not the T cell receptor. Hence, a proline-binding module dist inct from SH3 and WW domains regulates protein-protein interactions.