Background:After activation by phosphorylation, phospho-AKT (pAKT) is translocated to nucleus. Results: Ubiquitination of pAKT by NEDD4-1 is coupled to AKT activation at the plasma membrane by insulin-like growth factor (IGF)-1, which promotes pAKT nuclear trafficking. Conclusion: NEDD4-1 is an E3 ligase for pAKT specifically involved in pAKT nuclear trafficking in IGF-1 signaling. Significance: AKT activation and proper subcellular localization requires specific E3 ligases in a ligand-specific manner.
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