Protein tyrosine kinase regulation by ubiquitination: Critical roles of Cbl-family ubiquitin ligases

► Cbl-family ubiquitin ligases function as negative regulators of PTK signaling ► Recruitment and activation mechanisms ensure Cbl selectivity for activated PTKs ► Cbl-dependent ubiquitination regulates PTK degradation in lysosome and proteasome ► Genetic studies demonstrate essential roles of Cbl proteins in physiological pathways ► Mutational inactivation of Cbl is causally linked to human leukemia