Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway

The propagation of intracellular T cell receptor (TCR) signals involved various adapter proteins that are important molecular switches to connect proteins together. The global characterization of changes in protein-protein interactions following genetic perturbations is critical to understand the reorganization of protein networks associated with the observed phenotypes. Here, by combining genome editing techniques and AP-MS analysis we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the inactivation of each of the three GRB2-family adaptors. Our data define disruption context-specific and time-dependent networks that form around SLP76 after TCR stimulation, and selectively preserved or highly affected protein complexes that regulate T cell activation.