RIBP, a novel R1k/Txk- and Itk-binding adaptor protein that regulates T cell activation

A novel T cell-specific adaptor protein, RIBP, was identified based on its ability to bind Rlk/Txk in a yeast two-hybrid screen of a mouse T cell lymp homa library. RIBP was also found to interact with a related member of the Tec family of tyrosine kinases, Itk. Expression of RIBP is restricted to T and natural killer cells and is upregulated substantially after T cell acti vation. RIBP-disrupted knockout mice displayed apparently normal T cell dev elopment. However, proliferation of RIBP-deficient T cells in response to T cell receptor (TCR)-mediated activation was significantly impaired. Furthe rmore, these activated T cells were defective in the production of interleu kin (IL)-2 and interferon gamma, but not IL-4. These data suggest that RIBP plays an important role in TCR-mediated signal transduction pathways and t hat its binding to Itk and Rlk/Txk may regulate T cell differentiation.