The Casitas B-lineage lymphoma (Cbl) family of ubiquitin ligases has been studied for years regarding their important role in downregulation of ligand bound epidermal growth factor receptor (EGFR). The two isoforms c-Cbl and Cbl-b share the same structural features and are thought to be equally important for EGFR downregulation. Few comparative studies between c-Cbl and Cbl-b have been published with respect to EGFR regulation. Even though both Cbl proteins appear to display the same functional activity in EGFR regulation, some studies reveal that there might be some differences between these two isoforms. In this study, we have used biochemical studies and live imaging to further investigate and compare the recruitment and intracellular trafficking of c-Cbl and Cbl-b upon EGF stimulation.
Summarized, Cbl-b is recruited more efficiently to EGFR than c-Cbl upon receptor activation. However, this difference in recruitment does not seem to affect their trafficking, as both isoforms follow the same trafficking pattern to early endosomes.The finding that Cbl-b is recruited to the EGFR more efficiently than c-Cbl is recruited to the EGFR, implies that they could have distinct activities at early time points. Due to their important roles in downregulation of growth factor signaling, further investigations regarding their individual functions are of great importance.