Cbl proteins are a family of ubiquitin protein ligases (E3s) that negatively regulate signaling by targeting activated tyrosine kinases for degradation. Cbl- c is the most recently cloned member of the Cbl proteins and is expressed only in epithelial cells (the other Cbl proteins are ubiquitously expressed). Cbl-c, like the other mammalian Cbl proteins, can ubiquitinate the activated EGFR and target it for degradation. Through interactions with proteins containing SRC homology-2 (SH2) and SH3 domains, CBL proteins modulate downstream cell signaling.