Figure 2.

Schematic representation of the three main molecular mechanisms of CBL-mediated signal transduction modulation. (A) CBL is hypothesized to have a dual role in JAK2 signaling. On one hand, thanks to the interaction with the mediator LNK, CBL controls the ubiquitination and consequent degradation of JAK2, on the other hand it has been highlighted how the CBL-mediated ubiquitination at the JAK2 K970 residue causes JAK2 hyperphosphorylation and the consequent activation. (B) CBL is a well-known regulator of EGFR signaling, being able to induce EGFR ubiquitination and degradation. CBL binding can be mediated also by other adaptor proteins such as Grb2 and CIN85. (C) CBL activity also has a high influence on the PI3K/AKT signaling cascade. Through the interaction with LYN, it promotes the recruitment of PIK3R1 and the subsequent PI3K phosphorylation and activation.