The monomeric Casitas B-lineage lymphoma (c-Cbl, CBL) RING finger ubiquitin ligase (blue) can bind to phosphorylated RTK (orange peptide) via the TKBD domain. Upon phosphorylation, CBL undergoes a large conformational change that positions the ubiquitin-conjugating enzyme E2 (green) active site close to RTK. Cancer mutation sites are mapped on the structure of the complex and are shown in yellow; Zn ions are shown as blue balls. Other stages of the CBL activation cycle are depicted in Figure 1 of the article. For details, see article by Li and colleagues on page 561.