Ubiquitination and Regulation of Akt Activity

The serine/threonine protein kinase Akt (protein kinase B, PKB) is a member of the AGC family of protein kinases. Akt is involved in regulation of many different cellular processes, such as cell growth, survival, proliferation, apoptosis, metabolism and angiogenesis. There are three known Akt isoforms, Akt1, Akt2 and Akt3, which are closely related and widely expressed in mammals.

Activation of Akt includes several major steps. First, PI3K (phosphoinositide 3-kinase) phosphorylates PI (4,5)P2 (PIP2) toform PI(3,4,5)P3 (PIP3), which is required for the recruitment of Akt from the cytosol to the plasma membrane . The dual specificity protein phosphatase PTEN negatively regulates this process by dephosphorylating PIP3 to PIP2. 

At the membrane, Akt is phosphorylated at Thr308 within its catalytic domain by phosphoinositol-dependent kinase 1 (PDK1) and at Ser473 within its C-terminal regulatory domain by mammalian target of rapamycin complex 2 (mTORC2), resulting in its full activation.While regulation of Akt activity via Thr308 and Ser473 phosphorylation has been a subject of extensive research, much less is known about the effect of other posttranslational modifications (PTMs) on Akt activity. More recently, additional Akt regulatory PTMs were identified, including phosphorylation, acetylation, oxidation, glycosylation, SUMOylation and ubiquitination sites.Read more......