AKT phosphorylation sites of Ser473 and Thr308 regulate AKT degradation

Abstract

Protein kinase B (AKT) is a serine-threonine kinase that mediates diverse cellular processes in a variety of human diseases. Phosphorylation is always the best studied posttranslational modification of AKT and a connection between phosphorylation and ubiquitination has been explored recently. Ubiquitination of AKT is an important step for its phosphorylation and activation, while whether phosphorylated AKT regulated its ubiquitination status is still unknow. In the present study, we mimic dephosphorylation of AKT by using mutagenesis techniques at both Thr308 and Ser473 into Alanine (AKT-2A). After losing phosphorylation activity, AKT enhances its degradation and prevents itself release from the plasma membrane after insulin stimulation. Fourthermore, AKT-2A is found to be degraded through ubiquitin-proteasome pathway which declared that un-phosphorylation of AKT at both Ser473 and Thr308 sites increases its ubiquitination level. In conclusion, AKT phosphorylated at Ser473 and Thr308 sites have a significant effect on its ubiquitination status.