The mechanisms leading to the ubiquitination and degradation of the activated c-Abl kinase have not yet been identified. We found that the multi-adaptor protein ArgBP2 links c-Abl to the ubiquitin ligase Cbl. Phosphorylation of Cbl and ArgBP2 by c-Abl resulted in the stabilization of their interactions, thus facilitating Cbl-induced ubiquitination and subsequent degradation of c-Abl and ArgBP2.
- tyrosine kinase
Abbreviations used: Abl-KD, kinase-deficient Abl; Abl-SH2M, Abl SH2 domain mutant; ArgBP2, Arg-binding protein 2; Cbl-70Z, ubiquitin-ligase-deficient mutant of Cbl; CT, C-terminal; GST, glutathione S-transferase; HA, haemagglutinin; PY, phosphotyrosine; RF, ring finger; SH, Src homology; SoHo, sorbin homology.
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