Figure 3. c-Cbl may negatively regulate proximal signaling.

Engagement of the BCR activates Syk, resulting in the recruitment of LAB, which recruits c-Cbl to the complex, likely via an interaction with Grb2. In the absence of LAB, proximal signaling events are enhanced, suggesting that c-Cbl may negatively regulate proximal signaling. c-Cbl has been shown to negatively regulate Syk activation, and BCR and LAB have been shown to be ubiquitinated (Ub). However, it is unknown whether degradation, recycling, or just negative regulation of the proteins in this signaling complex occurs and whether this is c-Cbl-mediated.