Ligand-induced downregulation of TrkA is partly regulated through ubiquitination by Cbl

► c-Cbl can promote ligand-induced ubiquitination and consequent degradation of TrkA. ► TrkA ubiquitination and degradation required direct interactions between c-Cbl and phosphorylated TrkA. ► c-Cbl can induce downregulation of NGF-TrkA complexes through ubiquitination and degradation of TrkA. ► c-Cbl has little effect on the internalization of TrkA.